HighMag

February 9, 2012

2012-02-09T07:00:00.002-05:00

We all know that exercise is good for our bodies, and when we hear people talking about it in the media, the benefits are discussed in big-picture terms. A recent paper describes the effects of exercise at the cellular level, and gives me new motivation to get my ass in gear. Well, after I finish this heart-shaped Dunkin’ Donut (don’t give me that smug look…you know it’s delicious).

Autophagy is the process in which a cell metabolizes its own organelles and proteins. Autophagy takes place in the lysosome at a normal rate to rid the cell of old organelles, but is induced at higher rates in response to cellular stress to allow the cell to adjust to changing nutritional needs. A recent study finds that exercise can induce autophagy in muscle cells. In this paper, He and colleagues tracked autophagy in mice after they ran on treadmills. As seen in the images above, the number of autophagosomes (green dots) in the tibialis anterior muscle was higher in mice after 80 minutes of exercise (right), compared to before the exercise (left). Mice with a genetic mutation that prevented exercise-induced autophagy had lower endurance for exercise and had altered glucose metabolism. These fascinating findings provide us with a cellular understanding of how exercise prolongs life and protects our bodies from diseases such as diabetes and cancer.

He, C., Bassik, M., Moresi, V., Sun, K., Wei, Y., Zou, Z., An, Z., Loh, J., Fisher, J., Sun, Q., Korsmeyer, S., Packer, M., May, H., Hill, J., Virgin, H., Gilpin, C., Xiao, G., Bassel-Duby, R., Scherer, P., & Levine, B. (2012). Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis Nature, 481 (7382), 511-515 DOI: 10.1038/nature10758
Adapted by permission from Macmillan Publishers Ltd, copyright ©2012

February 6, 2012

2012-02-06T07:00:00.001-05:00

Watching your child learn to crawl, you realize how much coordination she needs to get up on all fours and move forward, working both sides of her body. You are convinced that your child is totally gifted and brilliant. Well, I have news for you…cells have a lot more to sort out in order to crawl. As you sheepishly compare your child’s brilliance to a cell and admit defeat (except for me, of course…my daughter really IS brilliant), take a moment to look at today’s beautiful images from a paper on cell migration.

When a cell is crawling, it first reaches out using membrane protrusions. At the leading edge of these protrusions, the cell will adhere to the underlying matrix. These nascent adhesions serve as anchors to the surface and give the crawling cell traction. Cell-matrix adhesions go through dynamic cycles of formation as nascent adhesions, maturation into focal adhesions, and turnover using a well-studied set of cytoskeletal proteins and regulators, but how these adhesions form and mature is not completely understood. Lawson and colleagues recently published results showing that a protein called FAK (focal adhesion kinase) promotes the recruitment of an adhesion protein called talin to nascent adhesions. Talin binds to integrin, a key adhesion protein, and was previously thought to recruit FAK to nascent adhesions. In the images above, a control cell (left) shows localization of talin (green) to nascent adhesions (red). However, without FAK (right), talin is not recruited to nascent adhesions.

Lawson, C., Lim, S., Uryu, S., Chen, X., Calderwood, D., & Schlaepfer, D. (2012). FAK promotes recruitment of talin to nascent adhesions to control cell motility originally published in the Journal of Cell Biology, 196 (2), 223-232 DOI: 10.1083/jcb.201108078

February 2, 2012

2012-02-02T07:00:00.005-05:00

When a cell makes it all the way to cytokinesis, it has already achieved greatness. DNA replication and mitosis are Big Deals, but a cell exits mitosis only to find itself in front of that final all-uphill mile of the New York City Marathon (even as a kid watching it, I thought that was so cruel). There is a lot of regulation and reorganizing that happens for a cell to correctly complete cell division and physically split into two cells, and a recent paper sorts out how membrane trafficking proteins are coordinated during the process.

Cytokinesis is the final step of cell division, when the two daughter cells are physically divided. At the start of cytokinesis, a contractile ring forms around the center of the dividing cell and begins to tighten. These contractions result in a cleavage furrow forming and pinching the dividing cell, after which only an intercellular bridge connects the two new daughter cells. With all of this contracting and pinching of the plasma membrane, it is no surprise that membrane trafficking proteins are important during cytokinesis. A recent paper looks at how endocytosis and membrane trafficking pathways are coordinated during cytokinesis. Specifically, Chesneau and colleagues found that Rab35 GTPase, an endocytic protein known to also be important in cytokinesis, is negatively regulated by ARF GTPase. ARF mutants (ones that are stuck in the activated GTP state, for those paying attention) have cytokinesis defects similar to Rab35 mutants (stuck in the inactive GDP state), including a failure after cleavage furrow progression and an instability of intercellular bridges. A seen in the images above, both the ARF mutant (bottom) and Rab35 mutant (middle) mislocalize a protein called SEPTIN2 (green, arrowheads), which is a cytoskeletal element that provides structure during cytokinesis. In a normal cell (top), SEPTIN2 is localized at the cleavage furrow.

Chesneau, L., Dambournet, D., Machicoane, M., Kouranti, I., Fukuda, M., Goud, B., & Echard, A. (2012). An ARF6/Rab35 GTPase Cascade for Endocytic Recycling and Successful Cytokinesis Current Biology DOI: 10.1016/j.cub.2011.11.058

January 30, 2012

2012-01-30T07:00:00.000-05:00

As the flu pins you to your bed this winter, take a feverish minute to thank the biologists who help us understand the virus that causes it, the influenza virus. And maybe make a promise to yourself that next year you’ll spend 10 minutes to get the vaccine.

Influenza is an RNA virus that causes fever, chills, pain, fatigue, and general misery. After the virus replicates inside a host cell, it assembles at the cell’s plasma membrane. Virus particles then bud from the cell’s plasma membrane, taking some of the membrane with it, and search for the next cell to invade. A recent paper describes the membrane composition of recently produced influenza virus particles, and suggests lipid raft involvement in influenza virus assembly. Lipid rafts are specialized membrane domains that float freely in the plasma membrane, and have a distinct composition of proteins and lipids (specifically sphingolipids and cholesterol) compared to the rest of the plasma membrane. In this paper, Gerl and colleagues quantified the lipid compositions for the host cell’s total membrane, the host cell’s apical membrane (where virus particles bud from), and influenza particles budded from these cells. The virus particles contained more sphingolipids and cholesterol than the host cell’s total or apical membrane, consistent with a model of virus budding from lipid rafts on the apical membrane. The electron micrographs above show purified spherical influenza virus particles recently budded from host cells.

Gerl, M., Sampaio, J., Urban, S., Kalvodova, L., Verbavatz, J., Binnington, B., Lindemann, D., Lingwood, C., Shevchenko, A., Schroeder, C., & Simons, K. (2012). Quantitative analysis of the lipidomes of the influenza virus envelope and MDCK cell apical membrane originally published in the Journal of Cell Biology, 196 (2), 213-221 DOI: 10.1083/jcb.201108175

January 26, 2012

2012-01-26T07:00:00.002-05:00

There are so many images that are in our collective memory…images that mark historic and significant events. There are the photos of Tiananmen Square, the “Migrant Mother” from the Great Depression, Abbey Road, etc. Well, cell biologists have our own images that stick in our collective memory. One of those more recent images is the “Svitkina image” of actin filaments, which I’ve mentioned before. So, when I saw that the Svitkina lab published a paper recently, I knew I had to share!

Cell-cell junctions are crucial for development, tissue structure, and cell-cell communication. One type of cell-cell junction is the adherens junction (AJ), which is a cadherin-based junction that links to the actin cytoskeleton within the cell. Although AJs are well-studied structures, how they assemble is still not completely known. A recent paper looks at the underlying actin filaments in developing AJs. According to Hoelzle and Svitkina, a junction is formed first by neighboring cells’ lamellipodia, sheet-like membrane extensions. Next, the two cells are connected by cadherin on thin bridges that look similar to filopodia, which are finger-like actin projections. Interestingly, these bridges form by actin filament growth from the rear-side of the lamellipodia towards the cell periphery. The images above are transmission electron micrographs of actin filaments in a bridge that connects two different cells (each cell labeled a different color in middle image). Gold beads (yellow, right image) found at the far ends of each cell’s bridge label VASP proteins, which are markers for filopodia.

Hoelzle, M., & Svitkina, T. (2011). The cytoskeletal mechanisms of cell-cell junction formation in endothelial cells Molecular Biology of the Cell, 23 (2), 310-323 DOI: 10.1091/mbc.E11-08-0719

January 23, 2012

2012-01-23T07:00:00.001-05:00

The mammalian brain has billions of synaptic connections, which is more than a little difficult to sort and map out. Today’s image is from a group of biologists who used their own brilliant synaptic connections and developed a technique for mapping out these connections in mammals.

One of the most commonly used fluorescent markers in cell biology is GFP, which stands for Green Fluorescent Protein. Scientists have been very creative in using this powerful tool to understand more about cell biology. For example, GRASP (GFP reconstitution across synaptic partners) is a technique developed a few years back in order to map out synaptic connections in worms and flies. In GRASP, one half of the GFP protein is expressed in one type of neuron, while the other half of GFP is expressed in a different type of neuron. Alone, each of these GFP fragments cannot fluoresce, but when the two neurons are close together in a synaptic connection, the GFP will fluoresce green light that pinpoints the location of a connection. Recently, a group of biologists made major modifications in this technique in order for it to work in mammals, whose synaptic architecture can vary a lot from flies and worms. In the images above, dendrites (red) in a mouse brain intersect with axons (blue), as seen as the green GRASP signal.

Kim, J., Zhao, T., Petralia, R., Yu, Y., Peng, H., Myers, E., & Magee, J. (2011). mGRASP enables mapping mammalian synaptic connectivity with light microscopy Nature Methods, 9 (1), 96-102 DOI: 10.1038/nmeth.1784
Adapted by permission from Macmillan Publishers Ltd, copyright ©2011

January 19, 2012

2012-01-19T09:03:00.002-05:00

One of the first things you likely learned in your high school biology class was about cyclins, and their elegant and important discovery about 30 years ago. Cyclins are well-studied proteins that (you guessed it) cycle throughout the cell cycle and guide progress from one stage to the next. Today’s image is from a paper showing novel roles for a cyclin, and serves as a great reminder that no matter how much we may know about something, there are always new and exciting things to discover.

A cell must coordinate more than a handful of processes in order for cell division to occur correctly, and a group of proteins called cyclins helps to guide this process. Cyclin levels cycle throughout the cell cycle and activate kinases called Cdks, and together the cyclin-Cdk complexes trigger specific events. A recent paper discusses new results showing how a cyclin (Cyclin A2) regulates cytoskeletal organization and cell migration, independently of its binding to Cdk. According to Arsic and colleagues, depletion of Cyclin A2 causes a change in the distribution of actin filaments and an increase in cell migration. Cyclin A2 interacts with and activates RhoA, an actin regulator, which in turn negatively regulates migration. In addition, metastatic cancer cells show less Cyclin A2 expression than non-spreading tumor cells. In the images above, the distribution of actin (red) and focal adhesions (structures that link the cell to the underlying matrix, green) changes when Cyclin A2 is depleted (bottom row), when compared to control cells (top row).

Arsic, N., Bendris, N., Peter, M., Begon-Pescia, C., Rebouissou, C., Gadea, G., Bouquier, N., Bibeau, F., Lemmers, B., & Blanchard, J. (2012). A novel function for Cyclin A2: Control of cell invasion via RhoA signaling originally published in The Journal of Cell Biology, 196 (1), 147-162 DOI: 10.1083/jcb.201102085

MLK Day of Service

2012-01-16T07:00:00.000-05:00

In lieu of the usual Monday morning HighMag image post, today I'd like to encourage everyone to participate in the MLK Day of Service today. President Obama has called for all Americans to help our communities and neighbors...and as scientists (or science-lovers!), we have a lot to offer!

You can:
-Volunteer to tutor local kids in after-school programs
-Serve as a judge for local science fairs
-Offer local school kids to come in and tour or "work" in your lab (feeling really ambitious? then start an entire program for this!)
-Talk at a school about science and how freaking awesome it is
-Volunteer at a local science or natural history museum
-Become an "On-call scientist" with AAAS for human rights organizations in need of experts (click here)
-Send in your own cell biology images to The Cell Image Library, which helps educators to teach biology (click here)
-Donate to non-profits that support biology research and/or education, such as the ASCB, Carnegie Institute for Science, AAAS, or the Science Friday Initiative (to name just a few)
-Help educate your state/local representatives about science-related issues by writing letters (click here and here)

And, finally...
-Ooze science-coolness. Make it a personal goal to serve as an everyday advocate of science, progress, and education. Don't be afraid of speaking up as an expert or geeking out about science at dinner parties. Fight for your department to train, hire, and promote underrepresented minorities in science. Don't give your neighbor's little girl a princess dress for her birthday...give her an ant farm. Don't try to impress folks with fancy words like endoplasmic reticulum or kinetochore...make science accessible.

These examples don't include the myriad of other ways to help our communities, both science and non-science-related. Help honor the legacy of Martin Luther King, Jr. for all of 2012.

January 12, 2012

2012-01-12T11:07:00.003-05:00

For a little protein, the cell is a big place. Many times it’s necessary for proteins to be clustered together in order to get a job done. Today’s image is from a paper describing how E-cadherin gets clustered at adherens junction sites like a flock of 12-year old teeny-bopper girls at a Twilight movie.

Sheets of epithelial cells are polarized—one side of the epithelial sheet faces the inside/lumen of an organ or tissue, while the other attaches to a supportive basement membrane. The establishment and polarization of epithelial cells depends on adherens junctions (AJs), protein complexes that serve as cell-cell junction sites. AJs are composed of a transmembrane protein called E-cadherin that connects the junctions to the cell’s actin cytoskeleton. E-cadherin must be distributed on the cell’s plasma membrane for AJ assembly, but how it is brought to the membrane and/or clustered at certain sites is not fully understood. A recent paper finds an association between E-cadherin and the exocyst protein Exo70. The exocyst is a complex that brings proteins from the Golgi apparatus (where they are sorted) to the plasma membrane. According to Xiong and colleagues, Exo70 is required for E-cadherin clustering at the plasma membrane and for maturation of newly-formed AJs. Exo70 performs this feat through its association with a kinase that can interact directly with E-cadherin (PIPKIγ, for you membrane-junkies out there). As seen in the images above, this kinase (green) and Exo70 (red) both associate at the lateral membranes of epithelial cells, where AJs form. Top row shows the cells as if we are looking down onto the cells, while bottom row shows cells as if we were looking through the plane of cells.

Xiong, X., Xu, Q., Huang, Y., Singh, R., Anderson, R., Leof, E., Hu, J., & Ling, K. (2011). An association between type I PI4P 5-kinase and Exo70 directs E-cadherin clustering and epithelial polarization Molecular Biology of the Cell, 23 (1), 87-98 DOI: 10.1091/mbc.E11-05-0449

January 9, 2012

2012-01-09T07:52:00.003-05:00

As a reader of this blog, I bet you are simply dazzled by mitosis like I am. Or, you may be sick of mitosis and my love of mitosis images. If that’s case, then scram! Mitosis is one of the most photogenic events in a cell and today’s images support this widely-accepted claim.

During mitosis, a lot has to happen correctly for two daughter cells to have an equal number of chromosomes. The list of participating proteins is as long as my arm, and includes several kinases that regulate mitotic progression. Aurora B kinase participates in just about every major mitotic event—it regulates chromosome condensation, localizes to microtubules, functions in monitoring and ensuring chromosome attachment to the spindle, and is necessary for cytokinesis. The role of a similar kinase, Aurora A, is less clear, possibly due to differences in the techniques used in previous research that led to ambiguous or contradictory results. Hégarat and colleagues recently used a chemical genetic strategy to find that Aurora A kinase is important in chromosome alignment and segregation. In addition, Aurora A and Aurora B kinases cooperate together to coordinate chromosome segregation and microtubule dynamics. Images above show different mitotic cells after Aurora A kinase depletion (chromosomes are blue, spindle is green, spindle poles are red). Many of the cells appear normal, and may represent different stages of mitosis. Some cells displayed gross defects in spindle morphology, as seen as the presence of multipolar and monopolar spindles (bottom right two images).

Hegarat, N., Smith, E., Nayak, G., Takeda, S., Eyers, P., & Hochegger, H. (2011). Aurora A and Aurora B jointly coordinate chromosome segregation and anaphase microtubule dynamics originally published in The Journal of Cell Biology, 195 (7), 1103-1113 DOI: 10.1083/jcb.201105058

January 5, 2012

2012-01-05T09:11:00.003-05:00

Despite my two-year old daughter’s observation that gummy fruit snacks are great adhesive tools, the tissues in our body require something a bit more sophisticated to stick together. Different types of tissue need different specialized adhesion structures. For example, desmosomes function in heart and skin tissue, which are under a lot of mechanical stress. Today’s image is from a paper describing how some desmosome proteins get to the adhesion site.

Desmosomes are highly-ordered structures at the plasma membrane that adhere cells to one another, and play a crucial role in maintaining tissue integrity both during and after development. The adhesion properties of desmosomes are due to the presence of two different cadherin proteins, called Dsg and Dsc. A recent paper describes how these two cadherins are trafficked to desmosome adhesion sites. According to Nekrasova and colleagues, Dsg and Dsc are transported to desmosomes by two different kinesins, which are motors that walk along microtubules. Dsg is transported by kinesin-1, while Dsc is transported by kinesin-2. That each desmosome cadherin has its own transport pathway suggests that the assembly and function of desmosomes, and in turn adhesion, can be tailored throughout development and tissue remodeling. In the sequence of images above, Dsg (red, arrow) is migrating along microtubules (blue) towards the cell periphery.

Nekrasova, O., Amargo, E., Smith, W., Chen, J., Kreitzer, G., & Green, K. (2011). Desmosomal cadherins utilize distinct kinesins for assembly into desmosomes originally published in The Journal of Cell Biology, 195 (7), 1185-1203 DOI: 10.1083/jcb.201106057

Happy Holidays!

2011-12-22T07:00:00.001-05:00

HighMag will be taking a short break to celebrate the holidays! See you next year!

December 19, 2011

2011-12-19T07:00:00.005-05:00

Just when you think the mitotic spindle can’t get any more magical, the Ran pathway comes out and says, “I’m here, beyotch!” Today’s image is from a paper showing how kinetochore fibers are stabilized using a Ran-dependent mechanism.

The mitotic spindle is a complicated apparatus that functions to separate chromosomes during mitosis through the attachment of microtubules to kinetochores on chromosomes. Many of these microtubules are sourced from a pair of centrosomes on either side of the spindle, but there is a population of important microtubules that are not generated at centrosomes. These “acentrosomal” microtubules are instead generated by the presence of RanGTP around the chromosomes. The idea is that these microtubules are able to capture kinetochores easily by being nucleated so close to them. The other ends (minus ends) of these acentrosomal microtubules are focused near the centrosomes, and a recent paper describes how these microtubules are stabilized. A protein called MCRS1 is a RanGTP-regulated protein and is found at the minus ends of chromosomal and kinetochore microtubules, according to Meunier and Vernos. MCRS1 stabilizes kinetochore fiber microtubules, and without it, spindles are unstable. As seen in the images above, MCRS1 (middle row, green in merged) is localized to the minus ends of microtubules (top row, red in merged). MCRS1 localization is more obvious (arrow in higher mag image) when only kinetochore fiber microtubules are present (middle column) when compared with control (left column). When kinetochore fibers are absent (right column), so is MCRS1.

Meunier, S., & Vernos, I. (2011). K-fibre minus ends are stabilized by a RanGTP-dependent mechanism essential for functional spindle assembly Nature Cell Biology, 13 (12), 1406-1414 DOI: 10.1038/ncb2372
Adapted by permission from Macmillan Publishers Ltd, copyright ©2011

December 15, 2011

2011-12-15T07:00:00.002-05:00

Instead of fat-shaming our fat cells, we need to thank them for providing our bodies with essential energy. Lipid droplets play an important role in storing this fat and are quite dynamic. Today’s image is from a paper describing the dynamics that allow lipid droplets to grow.

Lipid droplets (LDs) are dynamic lipid storage organelles that participate in a variety of cellular processes. Lipid droplet misregulation has been linked to diseases such as diabetes and obesity. A recent paper sheds light on how LDs grow, and describes how an LD-associated protein called Fsp27 contributes to LD growth. Gong and colleagues found that Fsp27 is enriched at the points where two lipid droplets contact each other. Lipids are exchanged between the two LDs at these contact points, with a net lipid transfer from smaller to larger LDs that eventually results in the merging of the LDs. Images above are of adipocytes, which are specialized cells that store fat for energy, showing Fsp27 (red in all images) localization on lipid droplets (green in top row). The points where two LDs contact each other has an enrichment of Fsp27 (arrowheads). Other LD-associated proteins (green in middle, bottom rows), however, are not enriched at LD contact sites.

Gong, J., Sun, Z., Wu, L., Xu, W., Schieber, N., Xu, D., Shui, G., Yang, H., Parton, R., & Li, P. (2011). Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid droplet contact sites originally published in The Journal of Cell Biology, 195 (6), 953-963 DOI: 10.1083/jcb.201104142

December 12, 2011

2011-12-12T07:00:00.000-05:00

If you have ever lived or worked with me (or are that poor guy who is married to me), then you know that I like things neat and organized. Anything less will send me into a sad tailspin that involves boxed wine and Cheetos. Thankfully, there are enough stunningly beautiful examples of precision, order, and patterning throughout biology to make me happy….like, really happy. Today’s image is from a paper that describes how the different cells in a fruit fly’s eye arrange into the honeycomb pattern seen above.

One of the big questions in developmental biology is how groups of different cell types arrange themselves to form a functional organ. A fantastic model to study this question is the compound fruit fly eye, made of hundreds of ommatidia. A group recently looked at how the several cell types in the developing fly eye are able to reorganize themselves into their honeycomb lattice. The very precise local movements of these cells, according to Johnson and colleagues, require regulation by a protein called Arf6 GTPase in order to connect cell surface signaling with the cytoskeletal rearrangements required for cell motility. The adaptor protein, Cindr, is able to bind to and sequester Arf6 activators called ArfGAPs, which in turn prevents local Arf6 activity. Images above show the precise honeycomb organization in a normal fruit fly pupal eye. In the developing eye (shown chronologically from left to right), the cone cells (orange in cartoon) of each ommatidia are surrounded by a hexagon lattice of cells.

Johnson, R., Sedgwick, A., D'Souza-Schorey, C., & Cagan, R. (2011). Role for a Cindr-Arf6 axis in patterning emerging epithelia Molecular Biology of the Cell, 22 (23), 4513-4526 DOI: 10.1091/mbc.E11-04-0305

ASCB treat

2011-12-08T07:00:00.004-05:00

The American Society of Cell Biology (ASCB) is a huge organization of about 10,000 cell biologists. This organization is fantastic for not only the support of biology research, but also for its help in career development, discussions of women in the sciences, support of biology education at every level, and influence on public policy.

The ASCB holds an annual meeting that is the top meeting choice for many cell biologists. This year's meeting wrapped up earlier this week, so I figured I would devote today's blog post to a favorite meeting event--Celldance! This isn't a dance for cell biologists (go the International C. elegans meeting for that rad event that lets you boogie with Nobel laureates...I'm looking at you, Craig Mello!). Celldance is a competition for stunning images and movies of cells. Movies can be descriptive or experimental, new or old, or they can help describe a cellular event for students and the general public.

So, please enjoy a few of the 2011 Celldance winners (and check out past winners here), courtesy of ASCB:

First place award: Cancer Dance - a stunning look at what may contribute to malignancy in some cells (Submitted by Tsutomu Tomita of Timelapse Vision, Inc.)

Public outreach award: Animation of Chromosome Alignment and the Spindle Assembly Checkpoint - beautiful, with sparkly animation of the amazing kinetochore and spindle checkpoint that makes me think of Katy Perry's "Firework" video (Submitted by Bin He, Virginia Tech)

Check out the rest of the 2011 CellDance winners here.

BONUS!! ASCB also announced winners of the first World Cell Race! This race pitted multiple cell types from labs all over the world against each other on race tracks made of fibronectin. The fastest cells were bone marrow stem cells, which clocked in at 5.2 microns per minute (or 0.000204 inches per minute). Check out the World Cell Race homepage for a movie of cells racing.

December 5, 2011

2011-12-05T07:00:00.000-05:00

When I read papers like the one that gave us today’s image, I think that one day my wish of jumping into a cell to float in the cytoplasm wearing goggles and swimmies may actually come true. Physical manipulation of proteins gets me so excited about how far our tools and technology have come. In this paper, biologists physically yanked on actin filaments to show how tension affects the presence and function of an actin-modulating protein.

Actin has many regulatory proteins that do a variety of things, such as promoting filament nucleation, branching, and severing. Cofilin is a ubiquitous protein that functions in actin filament severing and reorganization. Cofilin binds to the actin filament itself and induces a slight twist in the actin, which makes it easily severed. A recent paper describes the use of optical tweezers and manipulations to show that the binding of cofilin to actin, and in turn its severing of actin, is regulated by tension in the filaments. Hayakawa and colleagues bound one end of an actin filament to a glass coverslip and manipulated the other end using optical tweezers. When the filament was put under tension, the actin filament was not severed (or it took longer, in some cases). In another manipulation, a fine glass pipette was used to pull bundles of actin. Tension applied to the actin filaments caused a drop in the binding rate of cofilin to actin filaments, as seen in the images above. Top row shows actin (left) and cofilin (right, fat arrows) in a tension-relieved actin bundle, while bottom row shows actin and reduced cofilin binding in an actin bundle that was stretched by 20%.

Hayakawa, K., Tatsumi, H., & Sokabe, M. (2011). Actin filaments function as a tension sensor by tension-dependent binding of cofilin to the filament originally published in The Journal of Cell Biology, 195 (5), 721-727 DOI: 10.1083/jcb.201102039

December 1, 2011

2011-12-01T07:00:00.001-05:00

There are a lot of times when I wish I was a fly on the wall during a totally awesome experiment I’ve read about. This is not one of them, but purely for my own safety. Today, I share with you a humbling and stunning image of the deadly Marburg virus, a virus so pathogenic it requires intense special handling and facilities.

The filovirus family is made of the Ebola and Marburg viruses, which cause deadly hemorrhagic fevers in humans and non-human primates. All filoviruses are single-stranded RNA viruses, yet their range of morphologies is an obstacle in understanding the structure and assembly of these viruses. In addition, the intense containment conditions (called biosafety level 4) required to work with these viruses make many techniques either difficult or impossible. A group of biologists recently jumped over all of these hurdles to image Marburg virus particles using a variety of electron microscopy techniques. Bharat and colleagues are the first to show a detailed 3-D structure of a biosaftely level 4 pathogen, both after release and during virus assembly within an infected cell. In addition, Bharat and colleagues determined the location of different viral proteins within the virus. Above is a cryo-electron microscopy image of Marburg virus particles. All three different morphologies—filamentous, 6-shaped, and round—have spine-like protrusions coming from the virus particle membrane (arrowheads). Inset image shows striations just under the membrane in a filamentous virus particle.

Bharat, T., Riches, J., Kolesnikova, L., Welsch, S., Krähling, V., Davey, N., Parsy, M., Becker, S., & Briggs, J. (2011). Cryo-Electron Tomography of Marburg Virus Particles and Their Morphogenesis within Infected Cells PLoS Biology, 9 (11) DOI: 10.1371/journal.pbio.1001196

November 28, 2011

2011-11-28T07:00:00.000-05:00

Asymmetric cell division results in two unequal daughter cells and without it, stem cells would not hold the attention of biologists, sick patients, politicians, and those loud nut-jobs who have more passion than knowledge. Check out today’s image, from a paper identifying a new protein complex important in asymmetric division.

Asymmetric division occurs throughout development, and is when a cell divides to result in two daughter cells that are unequal in size and/or cell fate. Part of this process is the establishment of the axis along which the cell will divide. Once this polarity is established, the mitotic spindle can line up accordingly. Fruit fly neural stem cells, called neuroblasts, divide asymmetrically to result in the birth of another neuroblast and a smaller ganglion mother cell, which eventually gives rise to neurons. A recent paper identifies a new role for a signaling complex in establishing neuroblast polarity. In this paper, Carmena and colleagues found that the Rap1–Rgl–Ral complex of proteins regulates polarity establishment in fruit fly neuroblasts, and works alongside other well-studied polarity proteins such as aPKC, Par6, and Pins. As seen in the images above, Rap1 (bottom row, green in merged; arrows) is enriched on only one side (apical side) of neuroblasts throughout division (DNA is in red).

Carmena, A., Makarova, A., & Speicher, S. (2011). The Rap1-Rgl-Ral signaling network regulates neuroblast cortical polarity and spindle orientation originally published in The Journal of Cell Biology, 195 (4), 553-562 DOI: 10.1083/jcb.201108112

Happy Thanksgiving!

2011-11-24T07:00:00.001-05:00

Happy Thanksgiving to the HighMag readers! Instead of an image today, here are a few words of thanks.

I'm thankful for so much this year...my amazing husband and his consistent "liking" of every single HighMag post on Facebook, my sweet 2-year old daughter who knows that I'll light up when she says "Mitosis, Mommy," and my scruffy dog who gives his silent support of all HighMag posts by napping at my feet while I write. I'm truly a lucky gal.

I'm thankful for you guys, for letting me amuse myself. I'm thankful that I get to share my love of beautiful cell biology images, thankful that you read my little nuggets of cell biology research, and thankful that you even like (sometimes) my attempts at wit. Again...lucky gal.

Science would be nowhere without those toiling away at the lab bench, debating at the chalk board, arguing for more grant money, teaching, and presenting their research. Thank you, scientists. And a special thank you to those scientists and journals who supported my use of their images on HighMag.

I would give you all a hug, but let's face it...deep down, we're all science nerds. So, an awkward handshake to say, "Thank you," and a promise that we'll get a beer together after the holidays.

November 21, 2011

2011-11-21T07:00:00.003-05:00

Just like two shy nerds falling in love with the help of a few Romulan ales and a Star Trek movie, sometimes proteins that are destined to be together need some help finding one another. Today’s very cool image is from a paper showing the formation of a processive myosin complex.

Myosin is the molecular motor that walks along actin filaments. The most abundant type of myosin is found in our muscles and is necessary for muscle contraction, yet there are many types of myosin that function in many diverse cell types and processes. Most myosins use their two head domains to “walk” along actin, yet one unusual myosin called Myo4p only has one head domain. Myo4p transports mRNA molecules and forms a complex with an adaptor protein called She3p, yet the Myo4p-She3p complex alone cannot walk on actin. Recently, Krementsova and colleagues reported that another protein called She2p recruits two Myo4p-She3p complexes to form a two-headed motor. She2p serves as the middleman between the two motors and the mRNA that it transports, and provides the entire complex with the ability for long-range and continuous transport of mRNA along actin. In the metal-shadowed electron micrographs above, purified Myo4p-She3p complexes remain single-headed in the absence of She2p (left). In the presence of She2p (right), the Myo4p-She3p motors were able to pair up and form V-shaped structures, indicating a two-headed motor.

Krementsova, E., Hodges, A., Bookwalter, C., Sladewski, T., Travaglia, M., Sweeney, H., & Trybus, K. (2011). Two single-headed myosin V motors bound to a tetrameric adapter protein form a processive complex originally published in The Journal of Cell Biology, 195 (4), 631-641 DOI: 10.1083/jcb.201106146

November 17, 2011

2011-11-17T07:00:00.003-05:00

A virus is both crafty and determined…pretty good for a non-living thing, right? Today’s image is from a paper discussing transport of the simian virus 40, which has some clever tricks up its little capsid sleeve to make the host cell help out with the viral infection.

Simian virus 40 (SV40) is a DNA virus that does not have its own membrane envelope, making transport into and around a cell a non-trivial task. SV40 first binds to a cell’s membrane, then uses endocytosis to enter the cell and travel to the endoplasmic reticulum (ER). From the ER, the virus penetrates the membrane to have access to the cytosol of the cell, where it can then reach the nucleus and replicate its genome. A recent paper describes this ER membrane penetration step, and reports that SV40 particles go through a major structural change within the lumen of the ER. According to Geiger and colleagues, this conformational change exposes a part of the minor viral protein VP2, which then embeds the virus into the ER membrane. This change attracts the cell’s own ERAD machinery, normally used to find and degrade misfolded proteins in the ER, which then allows the escape of the virus particles into the cytosol. Images above are electron micrographs of cells infected with SV40 for 2 (left), 6 (right), and 19 (bottom) hours. Early in the infection, virus particles are bound to endosomal or vesicle membranes (left, arrows). In the ER, the virus appears more compact (right, red arrows), indicating the structural change. Later, the ER membrane appears flattened around the virus particles (bottom, arrows).

Geiger, R., Andritschke, D., Friebe, S., Herzog, F., Luisoni, S., Heger, T., & Helenius, A. (2011). BAP31 and BiP are essential for dislocation of SV40 from the endoplasmic reticulum to the cytosol Nature Cell Biology, 13 (11), 1305-1314 DOI: 10.1038/ncb2339
Adapted by permission from Macmillan Publishers Ltd, copyright ©2011

November 14, 2011

2011-11-14T07:00:00.000-05:00

Just like Willy Wonka’s trained squirrels getting rid of the bad nuts, an epithelial sheet is able to push out a dying or unwanted cell, all while maintaining an intact barrier. Today’s image is from a paper describing how the direction of cell extrusion is regulated, and is from the same lab that provided a cell extrusion image featured earlier this year (check it out here).

When a cell is extruded from an epithelial sheet, it can be pushed either apically, into the lumen of the organ, or basally, further into the underlying tissue surrounding the organ. This direction is important—although most extruded cells are eliminated on the apical side, living cells that are extruded basally may affect development or become an invading cancerous cell. A recent paper describes results showing that the tumor suppressor protein APC can target microtubules to the cell base in order to drive apical extrusion. In addition, this function of APC is required in the cell that is being extruded, in turn controlling the direction of the actin contractions that squeeze the cell out of the epithelial sheet. Cells either without APC or with a mutated form of APC extruded on the basal side. In the images above, microtubules (green) in wild-type epithelial cells (left) are highly organized and oriented towards the cell being extruded (asterisk). In APC mutant epithelial cells (right), microtubules are reduced and disorganized around the extruding cell.

Marshall, T., Lloyd, I., Delalande, J., Nathke, I., & Rosenblatt, J. (2011). The tumor suppressor adenomatous polyposis coli controls the direction in which a cell extrudes from an epithelium Molecular Biology of the Cell, 22 (21), 3962-3970 DOI: 10.1091/mbc.E11-05-0469

November 10, 2011

2011-11-07T07:00:00.002-05:00

Mistakes happen. If you are as special as DNA, then you have someone to point out those mistakes and fix them for you. That sounds like your PI editing your manuscript, doesn’t it? Today’s stunning image is from a paper describing DNA repair in meiotic divisions.

When double-strand breaks happen to DNA, the cell has an efficient pathway that recognizes and repairs the breaks to both DNA strands. Two kinase proteins, ATM and ATR, play pivotal roles by phosphorylating numerous key proteins involved in this process. The roles of these two proteins are well-studied in mitosis, but their function in meiosis is not clear. Meiosis is the reductive cell division that results in gametes (ooctyes or sperm). A recent paper describes the role of ATM and ATR in the meiotic cell divisions of fruit fly ovaries. Both ATM and ATR phosphorylate a protein called histone H2AV at the site of DNA breaks, providing a handy and fluorescently-labeled output of ATM and ATR activity. Joyce and colleagues found that ATR plays a role in regulating the cell cycle checkpoint machinery that halts cell cycle progression in the presence of DNA breaks, while ATM is required for the DNA repair of meiotic double strand breaks. As seen in the images above, H2AV levels (red, phosphorylated and unphosphorylated) decreased in the developing oocyte (green) until it was almost undetectable by stages 4 and 5 of oogenesis (see bottom row for higher magnification). These results suggest that either ATM/ATR does not respond to DNA damage at these stages or that repair occurs before these stages (before the first meiotic division).

Joyce, E., Pedersen, M., Tiong, S., White-Brown, S., Paul, A., Campbell, S., & McKim, K. (2011). Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair originally published in The Journal of Cell Biology, 195 (3), 359-367 DOI: 10.1083/jcb.201104121

November 7, 2011

2011-11-07T07:00:00.000-05:00

Actin is that super achieving big man-or-woman on campus who seems to be involved in and excelling at everything. Even if you roll your eyes at actin’s achievements and wonder what actin ISN’T involved in, you’re secretly impressed and jealous. Today’s image is from a paper on axon guidance and the role of the actin regulators WAVE and WASP.

Like many developmental processes, the guidance and mobility of developing axons depends on a dynamic actin cytoskeleton. Because most neuronal networks are quite complex, the use of the fruit fly’s eye provides biologists with a genetically-tractable model for understanding axon growth and guidance. The fly’s eye is a compound eye—there are 750 individual eyes called ommatidia, each comprised of 8 light-sensitive photoreceptor neurons (R-cells). A recent study tests the roles of two actin nucleating regulators called WASP and WAVE in R-cell axon targeting. In this study, Stephan and colleagues found that a protein called Abi regulates WAVE by ensuring its membrane localization, where WAVE activates the Arp2/3 actin nucleating complex. While WAVE is required for R-cell axon guidance, WASP is not. The images above show R-cell axons (green) in flies with different genetic backgrounds. Wild-type flies (left) and wasp mutants (right) have regular patterns and spacing of axons, while wave mutants (middle) have bundled or clumped axons with irregular spacing.

Stephan, R., Gohl, C., Fleige, A., Klambt, C., & Bogdan, S. (2011). Membrane-targeted WAVE mediates photoreceptor axon targeting in the absence of the WAVE complex in Drosophila Molecular Biology of the Cell, 22 (21), 4079-4092 DOI: 10.1091/mbc.E11-02-0121

November 3, 2011

2011-11-03T07:00:00.000-04:00

I love a hidden picture task. I love looking at a picture of a crowded street scene and identifying the nerd in the red and white sweater (side note: would Waldo’s fashion choices put him in the hipster category these days?). In cell biology, a researcher has to sort through the crowded scene in a cell to find what he or she is looking for. Today’s image is from a paper describing the function of microtubule motors, a difficult job given the complexity and interdependence of the motors and their regulators.

Microtubule motors called dynein and kinesin move all sorts of material around the cell. The motor binds to its cargo, a membrane vesicle for example, and “walks” it along a microtubule until it reaches its destination, such as an endosome or lysosome in this example. With multiple motors in any given cell type and a slew of regulators for each, the understanding of an individual motor’s contribution is unclear. A recent paper helps to sort through this complexity. In this paper, Yi and colleagues used acute inhibition of dynein and its regulators, followed by precise tracking of particles in a cell. Following the inhibition of dynein, multiple cargoes rapidly disperse around the cell, suggesting a sharp drop in minus-end directed transport along microtubules. In the images above, the top row shows cells at the time of the dynein inhibition, while bottom row shows several minutes later. Lysosomes/late endosomes, early endosomes, Golgi, and injected adenovirus (left to right) all dispersed towards the cell periphery following dynein inhibition. Interestingly, Yi and colleagues also saw a gradual decrease in transport in the other direction (plus-end directed) following dynein inhibition, suggesting a possible global effect on transport.

Yi, J., Ori-McKenney, K., McKenney, R., Vershinin, M., Gross, S., & Vallee, R. (2011). High-resolution imaging reveals indirect coordination of opposite motors and a role for LIS1 in high-load axonal transport originally published in The Journal of Cell Biology, 195 (2), 193-201 DOI: 10.1083/jcb.201104076

October 31, 2011

2011-10-31T07:00:00.001-04:00

All storytellers want to tell their story all the way to its end. Imagine how unsatisfying most movies or books would be without their endings. What if Scout didn’t get to meet Boo Radley? How boring would The Sixth Sense be? How tragic would Toy Story 3 be?! In cell biology, telling a whole story in one paper, from protein to cell to animal, is a rare luxury given the time and difficulty of most techniques. Today’s image is from a paper with a well-rounded story about the role of a cell cycle protein in non-cell cycle-related business.

The cell cycle is driven forward by complexes made up of proteins called cyclins and cyclin-dependent kinases (Cdks). One cyclin called cyclin E functions in the G1 to S phase transition in the cell cycle, marking the start of DNA replication. Because of this role, cyclin E is typically found in only dividing cells. A recent paper describes the important role of cyclin E in non-dividing cells in the adult brain. In this paper, Odajima and colleagues found that cyclin E regulates synapse formation by inhibiting Cdk5. Cyclin E disruption in neurons causes the number of synapses and dendritic spines to drop. Finally, adult mice with cyclin E-deficient brains had impaired learning and memory. In the images above, non-dividing neurons from mouse brain show the presence of cyclin E (red) in both axons and dendrites, along with Cdk5. SynGAP and Synapsin I are post- and presynaptic markers.

Odajima, J., Wills, Z., Ndassa, Y., Terunuma, M., Kretschmannova, K., Deeb, T., Geng, Y., Gawrzak, S., Quadros, I., Newman, J., Das, M., Jecrois, M., Yu, Q., Li, N., Bienvenu, F., Moss, S., Greenberg, M., Marto, J., & Sicinski, P. (2011). Cyclin E Constrains Cdk5 Activity to Regulate Synaptic Plasticity and Memory Formation Developmental Cell, 21 (4), 655-668 DOI: 10.1016/j.devcel.2011.08.009
Copyright ©2011 Elsevier Ltd. All rights reserved.

October 27, 2011

2011-10-27T07:00:00.006-04:00

Apoptosis sounds like a brutal death for a cell—all of that blebbing, fragmentation, and destruction just gives me the willies. Most of the time, cells only go through apoptosis when absolutely necessary thanks to proteins such as Bcl-x_L. A recent paper finds a new, non-apoptosis role for Bcl-x_L in cell health and survival.

The Bcl-2 family is made up of proteins that can either drive or inhibit apoptosis, which is programmed cell death. Bcl-x_Lis a Bcl-2 family member that inhibits apoptosis by binding Bax, a pro-apoptosis family member, at the outer membrane of mitochondria. There, Bcl-x_L inhibits the release of cytochrome c, which during apoptosis serves to kick-start a cascade that destroys the cell. A recent paper finds an exciting new role for Bcl-x_Loutside of apoptosis. Chen and colleagues found Bcl-x_Llocalized to the inner mitochondrial membrane, contrary to previous opinion that it is only found at the outer mitochondrial membrane. At the inner membrane, Bcl-x_Lis important in maintaining the efficiency of the mitochondria by inhibiting excessive flux of ions across the inner membrane. The images above are electron micrographs of mitochondria. Antibodies that label Bcl-x_Lare bound to tiny gold beads, which are found at the inner membrane (black arrows), as well as the outer membrane (arrowheads) and adjacent membranes (line arrows).

Chen, Y., Aon, M., Hsu, Y., Soane, L., Teng, X., McCaffery, J., Cheng, W., Qi, B., Li, H., Alavian, K., Dayhoff-Brannigan, M., Zou, S., Pineda, F., O'Rourke, B., Ko, Y., Pedersen, P., Kaczmarek, L., Jonas, E., & Hardwick, J. (2011). Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential originally published in The Journal of Cell Biology, 195 (2), 263-276 DOI: 10.1083/jcb.201108059

October 24, 2011

2011-10-24T07:00:00.001-04:00

Breaking up is hard to do. Thankfully for us, breaking up is also very beautiful (in cells). Abscission is the final cleaving of two daughter cells at the end of mitosis, and is really quite stunning to see. So, enjoy today’s images!

Cytokinesis is the physical division of two daughter cells at the end of mitosis. The final step of cytokinesis is abscission, during which the small midbody that connects the two cells is finally cleaved. This process involves precise regulation of cytokinesis proteins; for example, the small GTPase RhoA is required during cytokinesis for the establishment and contraction of the cleavage furrow that develops to divide the cells, yet RhoA must be inactivated for abscission. A kinase protein called CIT-K (citron kinase) was previously shown to function as a downstream effector of RhoA activity, yet a recent paper describes results suggesting the converse—that CIT-K regulates RhoA activity. In addition, Gai and colleagues found that CIT-K also interacts with and regulates anillin, an actin scaffold protein crucial in cytokinesis. The images of midbodies above show the localization of either anillin (left, green) or RhoA (right, green), as well as DNA (blue) and microtubules (red). Compared with control cells (top row), anillin and RhoA were nearly undetectable at late stage midbodies in cells lacking CIT-K (bottom row).

Gai, M., Camera, P., Dema, A., Bianchi, F., Berto, G., Scarpa, E., Germena, G., & Di Cunto, F. (2011). Citron kinase controls abscission through RhoA and anillin Molecular Biology of the Cell, 22 (20), 3768-3778 DOI: 10.1091/mbc.E10-12-0952

October 20, 2011

2011-10-20T09:25:00.002-04:00

One man’s trash is another man’s treasure. Photobleaching is an unavoidable side effect of imaging that leads to weakened fluorescent signals. Most of us pooh-pooh photobleaching, but some clever cell biologists use photobleaching as a fantastic tool instead. Today’s image is my new favorite use of photobleaching.

Glial cells function in the nervous system to support neurons and their signal transmission. Schwann cells are glial cells found at the neuromuscular junction (where neurons signal to muscles), and monitor the neurotransmission exchanged. Schwann cells can even function to form and regenerate the neuromuscular junction. A recent paper describes how Schwann cells establish their arrangement around the neuromuscular junction. In this paper, Brill and colleagues labeled individual Schwann cells and used live imaging to monitor their positioning. Schwann cells are dynamic during development, finding their appropriate position by competing for space with other Schwann cells. Schwann cells in adult animals, however, are much more static. In the images above, individual Schwann cells (pseudo-colored yellow, blue, white, and purple) were labeled by sequentially photobleaching one cell at a time, leading to distinct levels of fluorescence in each cell. The axon of the neuromuscular junction is in green. The Schwann cells are very dynamic in young mice (left) compared with adult mice (right), seen as the frequent formation and retraction of cell protrusions (arrowheads in the images of the boxed regions).

Brill, M., Lichtman, J., Thompson, W., Zuo, Y., & Misgeld, T. (2011). Spatial constraints dictate glial territories at murine neuromuscular junctions originally published in The Journal of Cell Biology, 195 (2), 293-305 DOI: 10.1083/jcb.201108005

October 17, 2011

2011-10-17T07:00:00.003-04:00

A cell biologist’s most valuable asset is his or her toolbox…the collection of techniques and methods they can use to ask a question about a cell. For example, to figure out how important a given protein is in a specific process, there are many options…good old fashioned deletion or mutation of its gene, chemical inhibition, imaging its localization, finding binding partners, etc. Varying results from each of these approaches can lead to confusion, but a good scientist can turn that confusion into a more fully developed understanding.

Angiogenesis is the formation of blood vessels off of existing vessels, and is a key process in development and tumorigenesis. VEGF (vascular endothelial growth factor) is a potent activator of angiogenesis, and Notch is a protein that converts endothelial cells into tip and stalk cells, which are cell types required for vessel formation. A research group found that function-blocking antibodies for VEGFR-3, a VEGF receptor protein, caused a decrease in angiogenesis in developing mice and in tumors. However, this same research group more recently found that complete deletion of the VEGFR-3 gene caused excessive branching and sprouting during angiogenesis, as well as decreased Notch signaling. By finding varying results with similar, but subtly different approaches, Tammela and colleagues were able to distinguish bimodal functions of VEGFR-3 during angiogenesis. In the images above, blood vessels lacking the gene for VEGFR-3 (left) have more branching than wild-type vessels (right). Vessels lacking VEGFR-3 also have more filopodia (yellow dots, bottom row), actin-rich protrusions used by tip cells to guide branching.

Tammela, T., Zarkada, G., Nurmi, H., Jakobsson, L., Heinolainen, K., Tvorogov, D., Zheng, W., Franco, C., Murtomäki, A., Aranda, E., Miura, N., Ylä-Herttuala, S., Fruttiger, M., Mäkinen, T., Eichmann, A., Pollard, J., Gerhardt, H., & Alitalo, K. (2011). VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling Nature Cell Biology, 13 (10), 1202-1213 DOI: 10.1038/ncb2331
Adapted by permission from Macmillan Publishers Ltd, copyright ©2011

October 13, 2011

2011-10-13T07:00:00.001-04:00

I started on my biology journey with my Ranger Rick subscription as a tiny kid (quickly followed by my Fisher-Price microscope). I loved wildlife, and felt heartbreak for declining populations of so many species. Now that I’m trying to pass along this conservation concern and love of animals to my F1, I’m excited to talk about how stem cells may help save the animals!

Some species have too few individuals to allow successful breeding and genetic diversity. For example, the drill is an endangered primate of Africa and the northern white rhinoceros is a critically endangered species with only 7 known individuals (that’s right…not 7 million or 7 thousand, just 7). A recent method paper describes the generation of induced pluripotent stem cells (iPSCs) from both of these endangered species. Ben-Nun and colleagues generated fully reprogrammed iPSC lines from cryopreserved fibroblasts. These cell lines had characteristics of pluripotent cells in other species (ie, alkaline phosphatase activity, Oct4, Sox2, and Nanog). Images above show differentiated embryoid bodies developed from the northern white rhinoceros’ iPSCs. These differentiated cells have markers for all three developmental germ layers, as indicated at the bottom of the image (SMA = smooth muscle actin). Future applications of these iPSCs are truly exciting. In addition to therapeutic uses for sick captive animals, iPSC-derived germ cells can help increase species numbers and diversity (in combination with assisted reproduction).

Friedrich Ben-Nun, I., Montague, S., Houck, M., Tran, H., Garitaonandia, I., Leonardo, T., Wang, Y., Charter, S., Laurent, L., Ryder, O., & Loring, J. (2011). Induced pluripotent stem cells from highly endangered species Nature Methods, 8 (10), 829-831 DOI: 10.1038/nmeth.1706
Adapted by permission from Macmillan Publishers Ltd, copyright ©2011

October 10, 2011

2011-10-10T07:00:00.001-04:00

If you are a fellow child of the 80s, you probably visualize a fried egg when you think of drug addiction. Fried eggs are delicious, but the reality about drug use is much more devastating and sobering…all the way to the level of the dendrites on our neurons. A recent paper describes the use of psychoactive drugs to help identify regulators of dendrite morphology.

MicroRNAs (miRs) are RNA structures that regulate gene expression by preventing the translation of specific mRNA sequences into proteins. miRs function throughout development, notably in the morphology and function of dendritic spines, which are small neuronal processes important in the transmission of a neuron’s signals. Psychoactive drugs such as nicotine, cocaine, and amphetamines can trigger changes in neuronal structure and function, and a recent paper identifies miRs as regulators of these changes. Lippi and colleagues found altered levels of miR-29a/b after exposing mice to psychostimulants. Altered levels of these miRs affect synaptic transmission and dendritic spine morphology, as seen in the images above. Healthy dendrites (top, left) have a mix of spine morphologies (top, right). After transfection with miR-29a (bottom, left) or miR-29b (bottom, right), the proportion of mushroom-shaped dendrites dropped significantly. miR-29a/b increases the number of filopodial protrusions through its targeting of the Arp2/3 actin nucleation complex.

Lippi, G., Steinert, J., Marczylo, E., D'Oro, S., Fiore, R., Forsythe, I., Schratt, G., Zoli, M., Nicotera, P., & Young, K. (2011). Targeting of the Arpc3 actin nucleation factor by miR-29a/b regulates dendritic spine morphology originally published in The Journal of Cell Biology, 194 (6), 889-904 DOI: 10.1083/jcb.201103006

October 6, 2011

2011-10-06T07:00:00.002-04:00

Plants are underrepresented on this blog. Thankfully, this isn’t a food blog with only carnivorous cholesterol-thickened readers. But still, plants need representing (woot woot!) and today’s lovely images should help.

Plant cell communication is accomplished through the direct cell-to-cell transport of transcription factors, which are proteins that regulate gene expression. Just as in animal cells, plant development depends on these signals being relayed correctly. A recent paper describes how one transcription factor called SHR (SHORT-ROOT) is trafficked. Koizumi and colleagues identified a SHR-interacting protein called SIEL, which also associates with endosomes. Without SIEL, plant embryos arrest in early development. The images above are cross-sections of roots. Top root is normal, with one layer each of 8 endodermis (E) and 8 cortex (C) cells. SIEL mutants (middle, bottom) had multiple endodermis and cortex layers, each with more cells than in wild-type. The double arrows indicate the thickness of these tissue layers combined.

Koizumi, K., Wu, S., MacRae-Crerar, A., & Gallagher, K. (2011). An Essential Protein that Interacts with Endosomes and Promotes Movement of the SHORT-ROOT Transcription Factor Current Biology, 21 (18), 1559-1564 DOI: 10.1016/j.cub.2011.08.013
Copyright ©2011 Elsevier Ltd. All rights reserved.

October 3, 2011

2011-09-30T15:04:00.006-04:00

Behind every great mobile organelle is an equally awesome motor protein. The motor proteins dynein and kinesin move cargo along microtubules, and play crucial roles in countless cellular processes. A recent paper shows how these two motors cooperate.

The fungus Ustilago maydis grows into long hyphal cells in laboratory culture. Their use in cell biology is powerful, as their length and motor transport is reminiscent of human neurons. These long cells grow from the cell tip and have similarly oriented microtubules at either end of the cell. In the middle of the cell, microtubules overlap with opposite polarity. The polarity of these microtubules is important – dynein motors walk to one end of microtubules (the “minus” end), while most kinesin motors walk to the other (the “plus” end). A recent paper looked at how these two motors cooperate with each other in the motility of early endosomes in U. maydis cells. Schuster and colleagues found that while dynein is important for short-range motility, kinesin is important for long-range transport through the antipolar microtubule array in the center of the cell. Top image above shows the elongated hyphal cell with the nucleus in red. Bottom image shows the growth of microtubules by showing two consecutive time-points of EB1 (red then green), which is a protein found on the tips of growing microtubules. The two different insets show the antipolar growth of microtubules at the center (left inset), compared with the growth of similarly-oriented microtubules near the cell tip (right inset).

Schuster, M., Kilaru, S., Fink, G., Collemare, J., Roger, Y., & Steinberg, G. (2011). Kinesin-3 and dynein cooperate in long-range retrograde endosome motility along a nonuniform microtubule array Molecular Biology of the Cell, 22 (19), 3645-3657 DOI: 10.1091/mbc.E11-03-0217

September 29, 2011

2011-09-29T13:12:00.000-04:00

Would you rather solve a 302-piece or a 100 billion-piece puzzle? This is a question I like to throw out when I explain the power of model organisms at family gatherings. Worms have 302 neurons, while the human brain has about 100 billion (give or take a few). Today’s image is from a great example of how informative model organisms can be in understanding key processes in our bodies.

Neurons are made of axons and dendrites – axons transmit information, while dendrites receive it. While both processes are key to the formation of a healthy nervous system, very little is known about dendrite formation. A recent paper describes dendrite development, using an oxygen-sensing neuron in the worm C. elegans. Kirszenblat and colleagues showed that dendrite formation in the oxygen sensory neuron is dependent on Wnt signaling, which is frequently used throughout development. Specifically, the LIN-44/Wnt signal and its associated LIN-17/Frizzled receptor trigger the initiation and guidance of the dendrite independently of axon development. Images and cartoons above show the oxygen sensory neuron (green) in normal worms (top left) and Wnt mutants (all others). Arrows point to axons while the arrowheads point to dendrites, which are either absent or incorrectly formed in the mutants.

Kirszenblat, L., Pattabiraman, D., & Hilliard, M. (2011). LIN-44/Wnt Directs Dendrite Outgrowth through LIN-17/Frizzled in C. elegans Neurons PLoS Biology, 9 (9) DOI: 10.1371/journal.pbio.1001157

September 26, 2011

2011-09-26T07:00:00.004-04:00

Our cells ask a lot of our chromosomes. Chromosomes contain all of our genetic material, but are required to compact themselves into skinny little things that can be easily divided during cell division. Throw a terrible virus into the mix, and chromosomes start to have trouble with their duties.

During mitosis, duplicated chromosomes separate after receiving a signal allowing anaphase to begin. Until this signal is relayed, each pair of chromatids stays attached to one another by the cohesin protein complex. Premature chromatid separation was recently found in some types of white blood cells in HIV-infected people, and can lead to cells having an incorrect number of chromosomes. This same research group more recently showed that this HIV-induced premature chromatid separation is caused by Vpr, an HIV accessory protein. Vpr causes premature chromatid separation by disrupting the higher-order structure of DNA surrounding the centromere, the region where kinetochores allow attachment to the mitotic spindle. In the images above, the cohesin complex (pink, arrows) is found within the centromere of a control chromatid pair (left). In cells expressing the HIV accessory protein Vpr (right), the cohesin complex is absent from the centromere of a loosely-bound chromatid pair (arrowheads).

Shimura, M., Toyoda, Y., Iijima, K., Kinomoto, M., Tokunaga, K., Yoda, K., Yanagida, M., Sata, T., & Ishizaka, Y. (2011). Epigenetic displacement of HP1 from heterochromatin by HIV-1 Vpr causes premature sister chromatid separation originally published in The Journal of Cell Biology, 194 (5), 721-735 DOI: 10.1083/jcb.201010118

September 22, 2011

2011-09-22T07:00:00.001-04:00

I love it when worlds collide. I love the movies where a country boy falls for a city girl. Or a robot develops a friendship with a wookie. Hilarity typically ensues in the movies, but fantastic new ideas and questions result from the discovery of biological processes colliding. So, when I came across a recent paper that revealed new results on the relationship between endocytosis and adhesion, I was all over it.

Cell-cell adhesion is constantly adjusted throughout development, wound healing, and cancer metastasis. E-cadherin is the major adhesion molecule that functions in epithelial cell adhesion and polarity, and is linked to the actin skeleton (via α-catenin) and p120. The level of E-cadherin at the cell surface influences the adhesive strength between two cells, and this strength can be adjusted by internalization (endocytosis) of E-cadherin away from the cell surface. A recent paper discusses results showing how internalization of E-cadherin is regulated by Numb, a protein that interacts with endocytosis adaptor proteins and is important throughout development. Sato and colleagues found that Numb interacts directly with p120, and showed that impairment of Numb prevents E-cadherin internalization. The images above show cysts of epithelial cells. In control cysts (top rows), E-cadherin and p120 (red) were found at the basolateral cell-cell junctions. In cysts with reduced levels of Numb (bottom rows), both E-cadherin and p120 localized to the apical membrane region (blue) too.

Sato, K., Watanabe, T., Wang, S., Kakeno, M., Matsuzawa, K., Matsui, T., Yokoi, K., Murase, K., Sugiyama, I., Ozawa, M., & Kaibuchi, K. (2011). Numb controls E-cadherin endocytosis through p120 catenin with aPKC Molecular Biology of the Cell, 22 (17), 3103-3119 DOI: 10.1091/mbc.E11-03-0274

September 19, 2011

2011-09-19T07:00:00.003-04:00

“Shock and awe” may be a good strategy if you’re planning an attack on ne’er-do-wells, but it really is a terrible strategy if you’re fine-tuning a nervous system. Instead the nervous system uses diplomacy in its refinement, and a recent paper describes a savvy signaling pathway that does the job.

During development, the nervous system refines its connections through removal of neuronal processes and elimination of excess neurons. Neuron removal takes place through apoptosis, or programmed cell death, and depends on signaling by the JNK pathway. JNK signaling, however, also functions in the growth and homeostasis of neurons. A recent paper describes how neurons can translate these opposing JNK signals. A kinase protein called DLK is able to induce neuron degeneration and apoptosis through JNK signaling, without affecting the other roles of JNK. The images above show neurons from mouse embryos cultured two different ways (top, bottom). Neuron growth was robust after the addition of growth factor (left). When the growth factor was taken away in control cases (middle), axons degenerated. Without DLK (right), neurons were protected from degeneration.

Sengupta Ghosh, A., Wang, B., Pozniak, C., Chen, M., Watts, R., & Lewcock, J. (2011). DLK induces developmental neuronal degeneration via selective regulation of proapoptotic JNK activity originally published in The Journal of Cell Biology, 194 (5), 751-764 DOI: 10.1083/jcb.201103153

September 15, 2011

2011-09-15T11:12:00.003-04:00

There is something so gratifying about a light switch. My two-year old will pull a chair to our kitchen light switch to turn it on and off. Over. And over. And over again. Maybe that’s why I find phosphorylation so satisfying (and maybe why I have a headache). It’s a molecular switch, and the vast combinations of where, when, and how different proteins are phosphorylated can provide mind-numbing levels of regulation within a cell. Combine my appreciation for phosphorylation with my absolute love for early worm embryos, and you have today’s lovely images.

The one-cell stage worm embryo divides like many cells throughout development—asymmetrically. Asymmetric cell division results in two daughter cells with different developmental fates and frequently different sizes. For asymmetric cell division to take place in the early worm embryo, the entire mitotic spindle apparatus is moved towards one end of the cell, the posterior. A complex of polarity proteins (made of PAR proteins and the aPKC homolog PKC-3) functions upstream of an evolutionary conserved pathway of proteins (made of the NuMA homolog LIN-5 and G-protein signaling), and a recent paper finds the well sought-after link between these two pathways. In Galli and colleagues’ paper, they show that LIN-5 is phosphorylated by PKC-3. The position of PKC-3 at only one side of the cell results in the phosphorylation of LIN-5 only in that region, which in turns allows the mitotic spindle to position itself correctly. In the images above, one-cell stage worm embryos show staining for phosphorylated LIN-5 (top row, red in bottom row) during mitosis (spindle is in green, chromosomes in blue). Phosphorylated LIN-5 is enriched at higher levels at the anterior cortex (the left-hand side in each image) during earlier stages of mitosis.

Galli, M., Muñoz, J., Portegijs, V., Boxem, M., Grill, S., Heck, A., & van den Heuvel, S. (2011). aPKC phosphorylates NuMA-related LIN-5 to position the mitotic spindle during asymmetric division Nature Cell Biology, 13 (9), 1132-1138 DOI: 10.1038/ncb2315
Adapted by permission from Macmillan Publishers Ltd, copyright ©2011

September 12, 2011

2011-09-12T07:00:00.004-04:00

Scientists always try to design clever experiments, and cross their fingers for clear results. Sometimes a scientist is lucky with both, and results are so intuitive that even a second-grader can see that yes, podosomes are exerting a force able to contribute to cell movement. Check out today’s image, which shows podosomes and their influence on a substrate.

Podosomes are actin-containing structures found where a cell contacts a solid surface. Podosomes can cluster together to form ring structures, and are thought to contribute to the migration of some cell types. Recently, a group of biologists tracked podosome rings and employed some clever tricks to show that podosomes can provide force—specifically for spreading, migration, and retraction of a cell. In one experiment, Hu and colleagues placed osteoclasts (bone cells that remove bone tissue) onto a gel substrate that had beads distributed throughout. By watching how the beads displaced underneath a cell’s podosome rings, it became clear that podosome rings were providing a force that pushed the beads out towards the ring periphery. As seen in the images above, arrows show the direction of the substrate/bead movement while the fluorescent signal shows the actin within the podosome ring.

Hu, S., Planus, E., Georgess, D., Place, C., Wang, X., Albiges-Rizo, C., Jurdic, P., & Geminard, J. (2011). Podosome rings generate forces that drive saltatory osteoclast migration Molecular Biology of the Cell, 22 (17), 3120-3126 DOI: 10.1091/mbc.E11-01-0086

September 8, 2011

2011-09-08T07:00:00.001-04:00

So after lab meeting, I’m going to grab a drink at the plus end of a microtubule. I hear it’s a swingin’ place, with lots of cool things going on. I also hear a kinesin-8 is a real mover and shaker at the plus end, but you’ll have to check out today’s image to see for yourself.

The structure and function of the mitotic spindle depends on the amazing qualities of microtubules. Microtubules grow and shorten from their plus ends (mostly), which are the ends that reach out towards the periphery of the cell or chromosomes during mitosis. The plus ends of microtubules are hotspots of activity—plus-tip-tracking proteins bind to the plus ends of microtubules and can regulate the dynamics of each microtubule individually. A group recently found that a microtubule motor called KIF18B plays an important role in regulating microtubule dynamics at the plus end. According to Stout and colleagues, KIF18B controls the length of astral microtubules, which are those that extend towards the cell periphery, and does so by interacting with another well-studied plus-tip-tracking protein called EB1. Without KIF18B, cells have an increased number and length of microtubules. As seen in the images above, KIF18B (green) is on the ends of astral microtubules during different stages of mitosis, and EB1 (orange) is found on the ends of all microtubules. Microtubules are gray, and chromosomes are blue.

Stout, J., Yount, A., Powers, J., LeBlanc, C., Ems-McClung, S., & Walczak, C. (2011). Kif18B interacts with EB1 and controls astral microtubule length during mitosis Molecular Biology of the Cell, 22 (17), 3070-3080 DOI: 10.1091/mbc.E11-04-0363

September 5, 2011

2011-09-05T07:00:00.002-04:00

When you hear the word “angiogenesis,” do you start hissing? Many of us associate angiogenesis with tumors on their way to becoming malignant cancer. Well, if it weren’t for angiogenesis, we’d all be in trouble. Angiogenesis is the formation of blood vessels from pre-existing ones, and is a key process during development.

Blood vessels are the tubular structures that transport all of the good stuff in our blood. The formation of blood vessels depends on angiogenesis, the process in which vessels are created from pre-existing ones. Angiogenesis is a tightly regulated process, as the blood vessels in many organs have a stereotypic organization, abundance, and shape. For example, zebrafish embryos have a regular pattern of blood vessels sprouting from the aorta, along the trunk of the fish. A recent paper describes the importance of Semaphorin-PlexinD1 signaling in the organization of these blood vessels. According to Zygmunt and colleagues, Semaphorin-PlexinD1 signaling ensures the correct spatial distribution and number of blood vessels along the embryo’s trunk. Without correct Semaphorin-PlexinD1 signaling, too many vessels sprout along the aorta, as seen in the images above. Normal embryos (left) have a very regular pattern of blood vessels (green, "SeA") sprouting up, while embryos lacking Semaphorin-PlexinD1 signaling (right) have too many sprouts, with incorrect positioning.

Zygmunt, T., Gay, C., Blondelle, J., Singh, M., Flaherty, K., Means, P., Herwig, L., Krudewig, A., Belting, H., Affolter, M., Epstein, J., & Torres-Vázquez, J. (2011). Semaphorin-PlexinD1 Signaling Limits Angiogenic Potential via the VEGF Decoy Receptor sFlt1 Developmental Cell DOI: 10.1016/j.devcel.2011.06.033
Copyright ©2011 Elsevier Ltd. All rights reserved.

September 1, 2011

2011-09-01T07:00:00.002-04:00

The nuances of the economy are nothing compared with the nuances throughout biology, yet we don’t see our scientists screaming at each other on TV (instead we see researchers versus Jenny McCarthy…ugh!). Researchers take their arguments and evidence to respectable journals and state the facts, which aren’t always in black and white. Today’s stunning image is from a paper that clarifies how actin can prevent AND promote secretion.

Cells use regulated secretion to release certain material outside of the cell at specific times. This multi-stage process involves the production and packaging of the material into secretory granules, trafficking of the material around the cell, and exocytosis (release) of the material out of the cell. Past research complicated the understanding of how important actin is in regulated secretion—some indicates that actin prevents it, while some indicates that actin promotes it. Recently, a research group dove right into the cell to look at regulated secretion in one specific cell type, and clarified the nuances of actin’s prevention/promoting roles. Nightingale and colleagues found that secretory granules are anchored to actin filaments to prevent premature secretion. However, actin later supports secretion by forming a ring-like structure at the site of the secretory granule’s fusion at the plasma membrane. This ring then contracts to help the release of material out of the cell. In the images above, actin (green) is found on the secretory granules (red). The higher magnification images (right) of the boxed region show the actin rings (bottom) found on fused secretory granules (middle).

Nightingale, T., White, I., Doyle, E., Turmaine, M., Harrison-Lavoie, K., Webb, K., Cramer, L., & Cutler, D. (2011). Actomyosin II contractility expels von Willebrand factor from Weibel-Palade bodies during exocytosis originally published in The Journal of Cell Biology, 194 (4), 613-629 DOI: 10.1083/jcb.201011119

August 29, 2011

2011-08-29T07:00:00.002-04:00

It’s easy to be overwhelmed when learning about all that goes on during development. Then, you learn about the regularity and geometry seen throughout development (and biology in general) and that anxiety is washed away. I love seeing regular patterns and shapes throughout the biological world, and today’s image is a nice example of precision during development.

During development of a frog’s skin, there are two layers of cells. The top layer is made of cells that secrete mucus, and the bottom layer is made of cells that have cilia, or small hair-like projections. During skin development, these two layers intercalate and the resulting organization of mucus-secreting and cilia-containing cells is precise and predictable. A recent paper identified a role for a receptor protein called dystroglycan (Dg for short) in skin development. Dg is a critical receptor of basement membranes, which are regions that underlie tissues to provide signals and mechanical support. According to Sirour and colleagues, Dg gene expression is found in the bottom layer of cells in the developing skin of frog embryos. Loss of Dg function results in the disruption of skin development, specifically cell intercalation, cell-cell adhesion, and organization of the underlying matrix. As seen in the images above, the skin of control frog embryos have a precise flower-like arrangement of cells—a cilia-containing cell is surrounded by mucus-secreting cells (top). When Dg levels were reduced (bottom), that organization is disrupted.

Sirour, C., Hidalgo, M., Bello, V., Buisson, N., Darribere, T., & Moreau, N. (2011). Dystroglycan is involved in skin morphogenesis downstream of the Notch signaling pathway Molecular Biology of the Cell, 22 (16), 2957-2969 DOI: 10.1091/mbc.E11-01-0074

August 25, 2011

2011-08-25T07:00:00.002-04:00

I like to imagine that actin and microtubules duked it out one day over which was more important. Actin let microtubules have the mitotic spindle, as long as actin could have the leading edge. So, imagine how ticked off microtubules were to learn that actin was discovered a few years ago to play an important role in Golgi organization, a task long-associated with microtubules. Zoinks!

The Golgi apparatus is a ribbon-like network of membrane stacks that process and sort various material synthesized by the cell. Its organization near the nucleus of the cell is long-known to be dependent on the microtubule cytoskeleton, and a recent paper describes new results on how important the actin cytoskeleton is in Golgi organization, too. Zilberman and colleagues have shown that an actin polymerizing protein called mDia1 and its activator, RhoA, affects the organization of the Golgi network. Specifically, when active forms of either of these proteins were introduced into cells, the Golgi network dispersed over an area much larger than in normal cells. In the images above, the Golgi network (red) covers a larger area in cells with an active form of mDia1 (bottom) than in normal cells (top). The actin network is in green.

Zilberman, Y., Alieva, N., Miserey-Lenkei, S., Lichtenstein, A., Kam, Z., Sabanay, H., & Bershadsky, A. (2011). Involvement of the Rho-mDia1 pathway in the regulation of Golgi complex architecture and dynamics Molecular Biology of the Cell, 22 (16), 2900-2911 DOI: 10.1091/mbc.E11-01-0007

August 22, 2011

2011-08-22T07:00:00.004-04:00

There are some images that just stick with you. They might be beautiful, fascinating, or terrifying. For example, I’ll never forget when my former labmates told me to Google pictures of a teratoma. Seriously, don’t do it…wait, you just did, didn’t you? Unless you are a C. elegans worm, you won’t find today’s images terrifying…instead, you are likely to be utterly fascinated.

C. elegans are small 1mm-long roundworms that are used extensively in biology research. When the head of one of these worms is touched, its immediate response is to quickly back away from the touch. A recent paper describes how a fungus may have shaped the evolution of this behavior. Maguire and colleagues found that a predacious fungus called D. doedycoides capture larval stage worms by forming rings that constrict the worm passes through. There is a delay between when the fungus senses a worm passing through its ring and when it constricts to trap the worm. During this delay, the worm’s touch response can trigger the worm to quickly back out of the trap. However, there are some worms with mutations in its touch response—these worms are caught more efficiently by the fungus. Images above are electron micrographs of larval stage worms caught by the constricting rings of the fungus (left) and close-up images of the fungus’ rings before (top) and after (bottom) they are constricted.

BONUS!! Check out the authors’ video abstract, which includes movies of this predator-prey interaction, here.

Maguire, S., Clark, C., Nunnari, J., Pirri, J., & Alkema, M. (2011). The C. elegans Touch Response Facilitates Escape from Predacious Fungi Current Biology, 21 (15), 1326-1330 DOI: 10.1016/j.cub.2011.06.063
Copyright ©2011 Elsevier Ltd. All rights reserved.

August 18, 2011

2011-08-18T07:00:00.006-04:00

I bet you think you’re pretty good at wearing the many proverbial hats in your life. I bet you can align a laser, walk your dog, change a diaper, and play in your awesome band of cell biologists. Well, integrins will put your hat-wearing to shame! Integrins are very important proteins (VIPs!) that play huge roles in adhesion, signaling, polarity, cell migration, cell division, and differentiation. Today’s image is from a paper describing new data on integrin trafficking.

Integrins are membrane proteins that interact with the environment outside of the cell to regulate cell adhesion and signaling. As part of the cell’s plasma membrane, integrins are constantly being brought into the cell and recycled back to the cell surface. Understanding this process is important—the way that integrins are recycled back to the cell’s surface (or not) can dramatically affect a cell’s ability to move, adhere to other cells, divide, and invade (in the case of cells in a tumor). A recent paper by Mai and colleagues describes a protein called RASA1 in regulating integrin recycling back to the membrane. RASA1 binds to integrin on a site where another protein called Rab21 also binds. So, these two proteins compete—Rab21 bound to integrin prevents its recycling back to the cell surface, while RASA1 binding allows integrin to traffic back to the surface. In the images above, when levels of RASA1 were reduced (bottom), cells were able to migrate more efficiently to close a “wound” scratched across a layer of cells, as compared to control cells (top). Images on the left show the wound shortly after it was created, while images on the right are four hours later.

Mai, A., Veltel, S., Pellinen, T., Padzik, A., Coffey, E., Marjomaki, V., & Ivaska, J. (2011). Competitive binding of Rab21 and p120RasGAP to integrins regulates receptor traffic and migration originally published in The Journal of Cell Biology, 194 (2), 291-306 DOI: 10.1083/jcb.201012126

August 15, 2011

2011-08-15T07:00:00.002-04:00

You may live in many places throughout your life, but you have only one hometown. No matter what, your core is deeply affected by where you grew up (for me, that core is made of a fondness for fries covered with gravy, impassioned shouts of Bruuuuuce, and traumatic experiences with a teasing comb and hairspray…yes, that’s New Jersey). Just like us, a tumor is affected by its origin…its growth, malignancy, and responsiveness to treatment are all dependent on where the cancer cells came from. A recent paper tracks tumor growth to determine the origin of a certain type of tumor.

The countless types of cancer each come from different cell types. A tumor’s potential for growth, spreading, and treatment are heavily dependent on the tumor’s cell of origin. Malignant glioma is a deadly type of brain tumor, and a recent paper has determined the cell of origin for this cancer. Lui and colleagues used a technique called MADM (mosaic analysis with double markers) that mimics the genetic mutations seen in gliomas. This technique labels mutant cells green and normal cells red, enabling them to track how and when the mutant cells develop into tumors. These biologists started out with neural stem cells, which were suspected as the cells of origin for gliomas, yet found that cells called oligodendrocyte precursor cells (OPCs) are the cells of origin. The images above show mutant MADM neurons. Left and right images show MADM labeling of mutant (green) and normal (red) cells, while middle image shows the nuclei of cells (blue in merged).

Liu, C., Sage, J., Miller, M., Verhaak, R., Hippenmeyer, S., Vogel, H., Foreman, O., Bronson, R., Nishiyama, A., Luo, L., & Zong, H. (2011). Mosaic Analysis with Double Markers Reveals Tumor Cell of Origin in Glioma Cell, 146 (2), 209-221 DOI: 10.1016/j.cell.2011.06.014
Copyright ©2011 Elsevier Ltd. All rights reserved.

August 11, 2011

2011-08-11T07:00:00.004-04:00

“Our country is just so polarized these days,” I say as I shake my fist, then tell those pesky kids to get off of my lawn. “Polarized” doesn’t have to be a dirty word…in fact, if it weren’t for polarized epithelial cells we’d all be big puddles of cells lacking the ability to digest food, reproduce, circulate blood, or breathe. Today’s image is from a paper describing how septins guide microtubule organization in polarized epithelial cells.

Epithelial cells form sheets that line various organs throughout the body. These epithelial sheets are polarized, meaning the cells are not symmetrically organized. For example, our intestine is lined with a polarized epithelial sheet that must absorb nutrients from the intestine’s cavity in one side of the cell sheet, and then eventually guide those nutrients to blood vessels. A key step in the polarization of a cell is the organization of the microtubule cytoskeleton. Microtubules are organized in a radial array in rounded cells, while the microtubules in polarized epithelial cells are arranged along the lateral borders of the cells and in networks under the apical and basal membranes (top and bottom). A recent paper looks at the role of proteins called septins in guiding microtubule organization during the establishment of polarity. Septins are filamentous proteins known for their roles in cell polarity, but Bowen and colleagues were able to show a functional link between septins and microtubule organization. Specifically, two populations of septins allow microtubule growth, bundling, and capture in different regions of the cell. In the image above, thick septin filaments (left, green in merged) are seen colocalized with microtubules (middle, red in merged) in epithelial cells. Bottom images are higher magnification views of the boxed region.

Bowen, J., Hwang, D., Bai, X., Roy, D., & Spiliotis, E. (2011). Septin GTPases spatially guide microtubule organization and plus end dynamics in polarizing epithelia originally published in The Journal of Cell Biology, 194 (2), 187-197 DOI: 10.1083/jcb.201102076

Microscopy as art

2011-08-08T07:00:00.000-04:00

Most of us are aware and in awe of the images from the Nikon Small World image competition. In case you are not, prepare to experience the world of microscopy in a new way. Check out the Image Galleries for the past few years here.

The Cell: An Image Library

2011-08-04T07:00:00.006-04:00

If you love geeking out over the beauty of cells, you must check out The Cell: An Image Library. It's a site of images, videos, and animations of cells that are contributed by some of the world's best biologists. The Library is hosted by the American Society for Cell Biology, so you know it is a great resource.

Some favorites:

A famously beautiful image of an actin network known to many of us as "the Svitkina image" is here. This image got me excited about actin in a way I wasn't willing to admit for years, especially as a proud lover of microtubules.

A rat intestinal cell absorbing a fatty meal is here. Next time you're tempted to order that delicious Fettuccine Alfredo, maybe this image will convince you to order the salad instead.

A dividing cell in metaphase, using Fluorescence Speckle Microscopy to visualize microtubule dynamics and kinetochores is here. Ah, spindles (contented sigh).

An animation of kinesin walking on a microtubule is here. If you feel moved for interpretive dance, you're not alone...my old labmates have seen my performance of this animation.

HighMag is on summer break!

2011-08-01T07:00:00.004-04:00

Hi folks!

HighMag is going to take a few days for a summer break. This will give me an opportunity to reflect on the state of science and magnify my interest in cell biology, with high resolution and a low noise-to-signal ratio. Lastly, I'll put myself in proper alignment so I can properly illuminate the world of cell biology imaging. Get it?! Man, I'm funny.

In the meantime, I'll post a few odds and ends in the cell biology imaging world that should be fun to share. For now, you can sit back and enjoy one of my favorite clips of Ernie. He totally embodies the curiosity that a lot of us had as kids, and maintain today as scientists. So, if you are at the bench and sick of doing 50 minipreps just to find out that your cloning didn't work (again), maybe this will remind you of the romance that drove you to the science world in the first place.

July 28, 2011

2011-07-28T07:00:00.007-04:00

The centromere is the plate on which a kinetochore is served. That plate, however, is mysterious. Recently, a group of cell biologists dug into this mystery by forming kinetochores on chromosome regions not typically associated with kinetochores.

Kinetochores are multi-protein structures that serve as the sites of spindle attachment for each chromosome during mitosis. Kinetochores are assembled on regions of the chromosomes known as the centromere. Although the importance of the centromere has long been appreciated, the exact qualities of centromere-ness remain unresolved. Some past research shows that centromere location in budding yeast is based on DNA sequence, while other organisms rely on repeated DNA sequences or epigenetic marks (meaning not due to DNA sequence) to identify the location of a centromere. A recent paper describes a technique that triggers brief over-expression of one of those epigenetic marks—the protein CID (Drosophila CENP-A or CENH3 for those keeping score). After a pulse of this over-expression, chromosomes are coated with CID signal (green, middle image above), yet after a few generations of cell division, those CID marks are mostly cleared away (right image). The remaining CID marks (arrows), Olszak and colleagues found, became sites of new functional kinetochores. By monitoring the early steps of kinetochore formation, these biologists hope to understand how centromere position is determined.

Agata M. Olszak, Dominic van Essen, António J. Pereira, Sarah Diehl, Thomas Manke, Helder Maiato, Simona Saccani & Patrick Heun (2011). Nature Cell Biology 13,799–808. DOI: 10.1038/ncb2272.
Adapted by permission from Macmillan Publishers Ltd, copyright 2011

July 25, 2011

2011-07-25T07:00:00.003-04:00

They invade...they proliferate...they destroy. It sounds like the tagline for a terrible summer blockbuster starring Samuel L. Jackson and an animated sidekick voiced by one of the Kardashians, but it’s the tagline of something far more sinister and real. I’m talking about tumors. Today’s image is from a paper showing how a membrane protein called caveolin-1 can support tumor invasion.

Caveolin-1 is a membrane protein and a major component of caveolae, which are small membrane invaginations that participate in endocytosis. A recent paper finds that caveolin-1 also functions in cell elongation, migration, and invasion by remodeling a cell’s microenvironment (aka “stroma”). Specifically, Goetz and colleagues found that caveolin-1 affects stromal architecture by regulating the activity of Rho GTPase, a signaling protein frequently involved in actin dynamics. This caveolin-1-inspired remodeling of the stroma is significant for tumor biology, too—the stiffness, contractility, and general architecture of a tumor’s stroma can affect its growth, invasion, and metastasis. In the images above, tumor cells (green) were cultured in a 3D-gels with fibroblast cells (red) that expressed caveolin-1 (top row) or did not express caveolin-1(bottom row). When tumor cells were surrounded by caveolin-1-expressing cells, they were able to invade further into the gel.

Goetz, J., Minguet, S., Navarro-Lérida, I., Lazcano, J., Samaniego, R., Calvo, E., Tello, M., Osteso-Ibáñez, T., Pellinen, T., Echarri, A., Cerezo, A., Klein-Szanto, A., Garcia, R., Keely, P., Sánchez-Mateos, P., Cukierman, E., & Del Pozo, M. (2011). Biomechanical Remodeling of the Microenvironment by Stromal Caveolin-1 Favors Tumor Invasion and Metastasis Cell, 146 (1), 148-163 DOI: 10.1016/j.cell.2011.05.040
Copyright ©2011 Elsevier Ltd. All rights reserved.

July 21, 2011

2011-07-21T07:00:00.002-04:00

When I think of mitochondria, I’m faced with a minor bout of nausea when I remember struggling to memorize all of the steps to oxidative phosphorylation during college. Although my college memories of Napster and the Y2K problem are clearer than those of the citric acid cycle, I know how important mitochondria are. A recent paper describes how mitochondria are anchored throughout the cell.

Mitochondria are organelles that provide metabolic energy to the cell. Depending on the energy needs in different regions of the cell, mitochondria move around using actin- and microtubule-based motors and then anchor themselves in place. A recent paper describes how intermediate filaments bind mitochondria to regulate their distribution and anchor them within the cell. Intermediate filaments provide mechanical strength in many cell types by forming rope-like networks of filaments, and are frequently made of a protein called vimentin. Nekrasova and colleagues found that in cells lacking vimentin, mitochondria were highly mobile within the cell. Images above show the colocalization of mitochondria (purple) and vimentin intermediate filaments (green) in mammalian cells. Middle and right images are higher magnification frames of the boxed regions.

Nekrasova, O., Mendez, M., Chernoivanenko, I., Tyurin-Kuzmin, P., Kuczmarski, E., Gelfand, V., Goldman, R., & Minin, A. (2011). Vimentin intermediate filaments modulate the motility of mitochondria Molecular Biology of the Cell, 22 (13), 2282-2289 DOI: 10.1091/mbc.E10-09-0766

July 18, 2011

2011-07-18T07:00:00.003-04:00

BAR domains are not just regions in a cell where proteins gather for a pint after a long day of cell division, migration, and sorting. No, BAR domains are regions on certain proteins that are able to bend membranes. This comes in handy for vesicle formation during endocytosis, and according to a recent paper, for plasma membrane organization.

Eisosomes are regions on the plasma membrane in budding yeast that are important for plasma membrane organization. They are positioned at the plasma membrane, where they sort membrane proteins and signaling molecules into small membrane invaginations. There is a long list of proteins found at eisosomes, many of which are uncharacterized. A recent paper looks at the functions of two core eisosome proteins – Pil1 and Lsp1. Olivera-Couto and colleagues found that these two proteins contain BAR domains, which are able to sense and change the curvature of membranes. Images above are electron micrographs of liposomes, which are artificially made vesicles. Untreated liposomes (top) are round, while vesicles treated with purified Pil1 or Lsp1 (middle and bottom) had tubules (arrows) deformed from the vesicles, showing that these proteins are capable of bending membranes.

Olivera-Couto, A., Grana, M., Harispe, L., & Aguilar, P. (2011). The eisosome core is composed of BAR domain proteins Molecular Biology of the Cell, 22 (13), 2360-2372 DOI: 10.1091/mbc.E10-12-1021

July 14, 2011

2011-07-14T07:00:00.004-04:00

Do you spend your photon budget wisely? This is a question that a recent paper asks, and answers back with a new technique that produces images that will blow your socks off. Once you put your socks back on, check out today’s image.

Cellular imaging is a constantly evolving field made of biologists on a never-ending quest for higher resolution of structures and faster image acquisition of a living cell. There are several challenges to these demands. For example, cells are not pancake-thin. Current techniques use illumination that leads to background noise in an image due to excited out-of-focus light. In addition, these techniques can cause phototoxic effects on cells, and can photobleach the fluorescent tags used to mark structures. Biologists have addressed these problems by using plane-illumination microscopy, which uses a separate excitation lens positioned orthogonally to the detection objective lens, leading to a more confined excitation of the focal plane. Planchon and colleagues recently improved this technique by using thinner sheets of light to illuminate the sample. The images produced using this Bessel beam plane illumination are remarkable, and allow for very fast 3D imaging of living cells. Images above show filopodia on a HeLa cell (left column), and the membrane ruffles on a kidney cell (right group of images). Purple arrowheads point to vacuole formation by macropinocytosis.

BONUS!! For a movie of the filopodia in the image above, click here. For a movie of the membrane ruffles and vacuole formation, click here. For many other knock-your-socks-off movies, click here.

Planchon, T., Gao, L., Milkie, D., Davidson, M., Galbraith, J., Galbraith, C., & Betzig, E. (2011). Rapid three-dimensional isotropic imaging of living cells using Bessel beam plane illumination Nature Methods, 8 (5), 417-423 DOI: 10.1038/nmeth.1586
Adapted by permission from Macmillan Publishers Ltd, copyright 2011

July 11, 2011

2011-07-11T07:00:00.004-04:00

Without the bones in my fingers, my typing would look a lot like my toddler’s typing. Asdlijfpoaweif. Today’s image is from a paper looking at bone formation. This paper is a great and satisfying example of story that begins with a developmental question and ends with a cellular mechanism.

Osteoblasts are the cells responsible for generating bone tissue. They are differentiated from mesenchymal stem cells, and a recent paper identifies a role for pannexin 3 in this process. Pannexins are gap junction proteins, which means they form channels that allow material to be exchanged between cells, or between a cell and its extracellular space. On the cellular level, Ishikawa and colleagues found that pannexin 3 serves many purposes in osteoblasts—as a channel for calcium ions on the ER, as a channel for extracellular release of ATP, and as a channel for the exchange of calcium waves between cells. Image above shows a newborn mouse growth plate (left) that is stained for visualization of pannexin 3 (green) and an osteoblast marker (red).

Ishikawa, M., Iwamoto, T., Nakamura, T., Doyle, A., Fukumoto, S., & Yamada, Y. (2011). Pannexin 3 functions as an ER Ca2+ channel, hemichannel, and gap junction to promote osteoblast differentiation originally published in The Journal of Cell Biology DOI: 10.1083/jcb.201101050

July 7, 2011

2011-07-07T07:00:00.002-04:00

Totally tubular! If Bill and Ted had an excellent adventure in the human body, you can be certain that they’d learn about the most excellent tube structures throughout the body. From the veins that carry our blood to the branching tubules in our lungs, tubes are very important structures. A recent paper looks at the role of adhesion proteins during tubule formation.

During development, dramatic rearrangements of epithelial sheets results in the formation of branched tubules, as seen in kidney, lung, and mammary gland tissue. As one might expect, these rearrangements require coordination of several cellular events such as cell division, migration, polarization, and adhesion. A recent paper describes the role of two adhesion proteins, E-cadherin and cadherin-6, in tubule formation. Jia and colleagues found that cadherin-6 is important in inhibiting tubule formation, while E-cadherin is important in the formation of a tubule’s lumen (its inside cavity). Images above show the use of cell cysts as a model for epithelial tubule and lumen formation, with fluorescent tags showing a lateral marker (blue) and lumen-facing apical markers (green and red). Samples of control cysts, cysts without cadherin-6, E-cadherin, or both are shown (moving left to right). Although the mutant cysts appear abnormal, polarization was not disrupted in cysts without either cadherin (although multiple lumens are visible in cysts lacking E-cadherin). The polarization of cysts lacking both cadherins, however, was completely disrupted.

Jia, L., Liu, F., Hansen, S., ter Beest, M., & Zegers, M. (2011). Distinct roles of cadherin-6 and E-cadherin in tubulogenesis and lumen formation Molecular Biology of the Cell, 22 (12), 2031-2041 DOI: 10.1091/mbc.E11-01-0038

June 30, 2011

2011-06-30T07:00:00.003-04:00

Between the high number of breast cancer patients and the pink ribbons seen all over, breast health is and will always be a hot topic. The breast is a fascinating system of different cell and tissue types, and today’s image is from a paper looking at a population of epithelial cells in the breast.

Breast tissue contains two layers of epithelial sheets—an outer layer of myoepithelial cells (MECS) and an inner layer of luminal epithelial cells (LECs). The LECs greatly expand during certain events, such as pregnancy and tumorigenesis, which results in either thinner or discontinuous coverage by the outer layer of MECs. Because of this, the MEC layer serves as an epithelial “gatekeeper,” by generating boundaries that help organize breast tissue. A recent paper looks at this gatekeeper function of MECs and finds that two proteins, SLIT and ROBO2, are important in regulating the proliferation of MECs. And, in turn, the growth of the MEC layer regulates the branching of mammary tissue. Image above shows mammary tissue in normal (left) or Robo mutant (right) mice. The loss of Robo leads to excessive branching (close-up views of boxed regions on bottom).

Macias, H., Moran, A., Samara, Y., Moreno, M., Compton, J., Harburg, G., Strickland, P., & Hinck, L. (2011). SLIT/ROBO1 Signaling Suppresses Mammary Branching Morphogenesis by Limiting Basal Cell Number Developmental Cell, 20 (6), 827-840 DOI: 10.1016/j.devcel.2011.05.012
Copyright ©2011 Elsevier Ltd. All rights reserved.

June 27, 2011

2011-06-27T07:00:00.001-04:00

In my grad school days, I was an asymmetric cell division aficionado. I loved the asymmetric cell division that I studied for those years, the one-cell stage worm embryo. With that statement out of the way, I can admit that I secretly coveted the extremely asymmetric divisions of ooctyes. Check out today’s lovely image of a mouse oocyte, from the cover of Current Biology.

Rather than dividing to produce two identical daughter cells, an oocyte divides to produce a large egg ready for fertilization and a very small polar body. This extreme asymmetric division allows the egg to retain all of the crucial cytoplasm to support a future early embryo. This asymmetry is necessary for fertility and development, but the mechanisms required for this event are not completely understood. A recent paper describes the importance of two novel actin nucleators called Spire1 and Spire2 in mouse meiotic divisions. These Spire proteins drive the assembly of an actin network that acts as a substrate for positioning of the meiotic spindle, and promotes the cytokinetic cleavage furrow that results in polar body extrusion. Image above shows a mouse oocyte undergoing a meiotic division—chromosomes are cyan, microtubules are blue, and cortical actin is red.

BONUS!! Check out this great movie showing spindle positioning in normal (left) and Spire-deficient (right) ooctyes.

To see the cover of Current Biology for this issue, which features the above image, click here.

Pfender, S., Kuznetsov, V., Pleiser, S., Kerkhoff, E., & Schuh, M. (2011). Spire-Type Actin Nucleators Cooperate with Formin-2 to Drive Asymmetric Oocyte Division Current Biology DOI: 10.1016/j.cub.2011.04.029
Copyright ©2011 Elsevier Ltd. All rights reserved.

June 23, 2011

2011-06-23T07:00:00.002-04:00

Life is a balance of giving and taking, and this starts with our cells. I’ve written about cells taking in material (endocytosis) plenty of times, but it’s time to talk about cells secreting material out of the cell. Check out today’s stunning image of salivary gland cells in the fruit fly larva.

All cells undergo some base level of secretion, but there are many cell types with specialized “regulated” secretion. For example, our endocrine cells secrete the hormones that regulate our bodies and throw teenagers into crazed states. Cells with regulated secretion store high concentrations of certain proteins in dense organelles called secretory granules, until there is a signal that triggers the release of these proteins. A recent paper asks how secretory granules are formed, and finds that two vesicle coat proteins, called AP-1 and clathrin, are required. Burgess and colleagues looked at secretory granules in larval fruit fly salivary glands, and found that AP1 and clathrin are localized at newly synthesized secretory proteins, Golgi structures (where the proteins are sorted), and maturing secretory granules. Images show salivary gland cells with AP1 (red) colocalizing with Golgi structures (green).

Burgess, J., Jauregui, M., Tan, J., Rollins, J., Lallet, S., Leventis, P., Boulianne, G., Chang, H., Le Borgne, R., Kramer, H., & Brill, J. (2011). AP-1 and clathrin are essential for secretory granule biogenesis in Drosophila Molecular Biology of the Cell DOI: 10.1091/mbc.E11-01-0054

June 20, 2011

2011-06-20T07:00:00.004-04:00

As you all vacation this summer at the beach, throw a “Thank you!” out to the sea urchins for their amazing contributions to cell and developmental biology research. Today’s image is from a paper showing a role for a major polarity protein in cilia formation in sea urchin embryos.

After a sea urchin’s initial stages of embryogenesis, it hatches out of its eggshell to become a swimming resident of the marine world. It swims using cilia, which beat to push water around. The cilia on this swimming embryo reside in the outer layer of epithelial cells, and emanate from basal bodies just below each cell’s surface. A recent paper shows a role for the polarity protein aPKC (atypical protein kinase C) in the formation of cilia in the sea urchin embryo. aPKC is a member of a protein complex important in asymmetric cell divisions, and Prulière and colleagues found that it has a very asymmetric localization during ciliogenesis. Images above show cilia (red) of sea urchin embryos in the absence (top left) or presence of an aPKC inhibitor. As the levels of the inhibitor increases (concentrations are indicated), the length of cilia decreases.

Pruliere, G., Cosson, J., Chevalier, S., Sardet, C., & Chenevert, J. (2011). Atypical protein kinase C controls sea urchin ciliogenesis Molecular Biology of the Cell, 22 (12), 2042-2053 DOI: 10.1091/mbc.E10-10-0844

June 16, 2011

2011-06-16T07:00:00.004-04:00

Glutamate is such an abundant and important neurotransmitter that I may just eat my weight in MSG-filled Chinese takeout tonight to get extra (honestly, I don’t recommend this). Today’s image is from a paper using kick-ass techniques to show how glutamate plays a role in dendritic spine formation.

Our neurons have dendritic spines that receive input signals. These spines are small protrusions that are formed and remodeled throughout development and as a result of learning and sensory experiences. A recent paper describes the identification of glutamate as a biochemical signal able to induce spine growth. In this paper, Kwon and Sabatini took high-resolution images of specific mouse neurons and then uncaged, or activated, a form of glutamate at specific spots on the neuron. At these spots of uncaged glutamate, dendritic spines formed de novo and were rapidly functional. Images above show two examples of mouse neurons on which glutamate was uncaged (yellow dots), leading to the appearance of new spines (arrowheads).

Hyung-Bae Kwon, & Bernardo L. Sabatini (2011). Glutamate induces de novo growth of functional spines in developing cortex
Nature, 474, 100-104 : doi:10.1038/nature09986
Adapted by permission from Macmillan Publishers Ltd, copyright 2011

June 13, 2011

2011-06-13T07:00:00.003-04:00

It’s true that yeast isn’t considered the most photogenic organism around because of their tiny size, but I shudder to think how far behind we’d all be if it weren’t for the amazing discoveries made using yeast. Today, please enjoy these stunning images of fission yeast from a paper describing actin polymerization during endocytosis.

Endocytosis is the process during which a cell takes in material from the outside. Membrane-bound vesicles form within the cell to transport material to its final destination. Like most things dynamic in a cell, actin plays a very important role. In yeast, actin patches form at sites of endocytosis to help in membrane invagination and scission, key processes that result in the formation of a vesicle. A recent paper found that a protein called dip1p is a crucial switch to initiate the formation of actin patches at sites of endocytosis in fission yeast. Images above show a reduction in the number of actin patches in yeast without dip1p (right), compared to wild-type yeast (left).

Roshni Basu, & Fred Chang (2011). Characterization of Dip1p Reveals a Switch in Arp2/3-Dependent Actin Assembly for Fission Yeast Endocytosis Current Biology, 21 (11), 905-916 : doi:10.1016/j.cub.2011.04.047
Copyright ©2011 Elsevier Ltd. All rights reserved.

June 9, 2011

2011-06-09T07:00:00.004-04:00

There are a lot of great horror movies around, but not a single one features GIANT MITOCHONDRIA! I’m going to call Hollywood directly and suggest a movie about giant mitochondria. Or, I could suggest you check out today’s image and fascinating paper on giant mitochondria in fruit fly sperm.

Sperm can grow quite long in the testes of male fruit flies, with some reaching 6 cm long. These elongated sperm have better success at fertilizing female fruit flies than shorter sperm. A recent paper looks at the cellular mechanisms that allow developing spermatids to grow to such great lengths, and the authors find that giant mitochondria play a very important role. Noguchi and colleagues found that growing mitochondria provide a platform for microtubules to grow in the elongating spermatids, and this combined structure serves as a template for cell shape. Image above shows microtubules (green) and mitochondria (red) in a fruit fly spermatid.

Tatsuhiko Noguchi, Michiko Koizumi, & Shigeo Hayashi (2011). Sustained Elongation of Sperm Tail Promoted by Local Remodeling of Giant Mitochondria in Drosophila Current Biology, 21 (10), 805-814 : doi:10.1016/j.cub.2011.04.016
Copyright ©2011 Elsevier Ltd. All rights reserved.

June 6, 2011

2011-06-06T07:00:00.005-04:00

The human body is amazing, but cannot hold a candle to many organisms when it comes to limb regeneration. Zebrafish are able to regenerate amputated fins, including the sensory axons in the fin that sense touch. Today’s image is from a paper discussing the signals required for this process.

When tissue is regenerated, there are several different cell types that must be involved in order to heal the entire tissue. A recent paper looks at the regeneration of skin cells and sensory neuron axons in zebrafish to determine how the process of wound healing requires the coordination of several cell types. Zebrafish larvae can regenerate both the skin tissue and sensory axons of an amputated tail fin, and Rieger and Sagasti found that the reactive oxygen species hydrogen peroxide (H2O2) plays an important role in this coordination. Injured skin cells release the H2O2 signal, and this signal then promotes robust regeneration of the sensory axons. Images above show the sensory axons in uninjured (top) and amputated (bottom) tail fins over time. Axons were regenerated into the amputated region (dotted line, shaded region), as seen as the red trajectories of axon tips (left-most image).

Rieger, S., & Sagasti, A. (2011). Hydrogen Peroxide Promotes Injury-Induced Peripheral Sensory Axon Regeneration in the Zebrafish Skin PLoS Biology, 9 (5) DOI: 10.1371/journal.pbio.1000621

June 2, 2011

2011-06-02T07:00:00.004-04:00

Alphabet soup is not tasty, but must be devoured by any researcher. Some of the acronyms in biology, though, stand out for their importance and FRAP is one of them. FRAP is a very handy technique for studying the dynamics of proteins in a cell, and the paper from today’s image is a great example of how elegant and informative FRAP can be.

Titin is an abundant muscle protein that provides structural support for the sarcomere, which is the basic contracting unit in muscle. There are many isoforms of titin that allow structural and mechanical changes of the muscle tissue throughout development and during disease. The sturdiness that titin provides muscles may give an impression of a lack of dynamics, but a recent paper shows exactly the opposite. The authors in this study use a technique called fluorescence recovery after photobleaching (FRAP). In this case, fluorescently labeled titin was photobleached using a high power laser. By watching if and how the photobleached region recovers new fluorescent titin over time, da Silva Lopes and colleagues concluded that titin is very mobile and dynamic. Titin maintains unrestricted movement around sarcomeres, and this movement is dependent on calcium. In the images above, two different sized regions (top, bottom) of fluorescently-tagged titin within sarcomeres were photobleached. In both cases, the bleached regions (arrowheads in middle images) quickly recovered the titin fluorescent label (right) to levels similar to pre-bleach images (left).

da Silva Lopes, K., Pietas, A., Radke, M., & Gotthardt, M. (2011). Titin visualization in real time reveals an unexpected level of mobility within and between sarcomeres originally published in The Journal of Cell Biology, 193 (4), 785-798 DOI: 10.1083/jcb.201010099

May 26, 2011

2011-05-26T07:00:00.002-04:00

“Bring out yer dead!” Thankfully, epithelial sheets have a much more efficient and beautiful way of clearing out dying cells than the famous Monty Python scene. Today’s stunning images are from a paper describing the signaling epithelial cells use to push out dying cells. It’s no wonder that the authors’ image made the cover of Journal of Cell Biology!

The function and health of an organ strongly depends on the integrity of the epithelial sheet protecting it. In order to preserve the epithelial barrier, dying cells are pushed out of the epithelial sheet in a precise and finely-tuned process called apoptotic cell extrusion. In this event, cells surrounding the dying, apoptotic cell form an actin and myosin ring that contracts to push the dying cell out of the sheet. A recent paper describes the signaling that takes place to initiate cell extrusion. The dying cell produces a signal called bioactive lipid sphingosine-1-phosphate (S1P), which activates actin-myosin contraction via its receptor (S1P2) in neighboring cells. The images above show epithelial sheets in normal and S1P2 mutant zebrafish larvae. In the mutant, the apoptotic cell (green) stays in the epithelial sheet and lacks the actin ring (red) seen in the wild-type tissue.

Gu, Y., Forostyan, T., Sabbadini, R., & Rosenblatt, J. (2011). Epithelial cell extrusion requires the sphingosine-1-phosphate receptor 2 pathway originally published in The Journal of Cell Biology, 193 (4), 667-676 DOI: 10.1083/jcb.201010075

May 23, 2011

2011-05-23T07:00:00.005-04:00

“Hooolllly crap, this is so cool!” was what I said to my (accountant) husband after I read this paper. I did an interpretive dance to describe the many cool things in this particular paper, and I know you will too. Today’s image is from a recent paper about understanding the cellular mechanisms that underlie the very complicated mental disorder schizophrenia.

Schizophrenia is a mental disorder characterized by disorganized thought processes and emotional dysfunction. There is a strong genetic component to the disorder, yet the basic cellular mechanisms that occur in schizophrenic patients is not completely understood. Past studies have looked at post-mortem brains, which have taught biologists a lot about what a schizophrenic’s brain looks like. These studies, however, cannot help pinpoint the specific cells affected by schizophrenia and the molecular mechanisms that lead to the disorder. A recent paper does amazing acrobatics to figure out these unknowns. In this paper, Brennand and colleagues took fibroblasts from schizophrenia patients who have a high likelihood of having a genetic component to their disorder. These fibroblasts were reprogrammed into pluripotent stem cells, and then differentiated into neural progenitor cells and neurons. These neurons had decreased connectivity, diminished numbers of neurites, and altered levels of many key neuronal proteins and signals (glutamate receptors, for example…a biggie for neurons). Images above show the difference in neuronal connectivity in the neurons induced from stem cells in healthy (left) and schizophrenic (right) patients.

Brennand, K., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., Li, Y., Mu, Y., Chen, G., Yu, D., McCarthy, S., Sebat, J., & Gage, F. (2011). Modelling schizophrenia using human induced pluripotent stem cells Nature, 473 (7346), 221-225 DOI: 10.1038/nature09915

Adapted by permission from Macmillan Publishers Ltd, copyright 2011

May 19, 2011

2011-05-19T07:00:00.002-04:00

If you read this blog, then you were probably the type of kid who used your toy microscope to look at the wound on your knee caused by your brother pushing you onto the ground (for example). You could see the skin around the scab stretching, and you knew there was some cool stuff going on there. I’m not sure if the authors from today’s image did this, but in a very sophisticated way they do now.

Our cells and tissues are equipped with the ability to repair wounds caused by normal wear-and-tear and injury. When the plasma membrane of a single cell is torn, the membrane and underlying cytoskeleton must be repaired. A recent paper describes the use of early fruit fly embryos to understand what occurs during single-cell wound repair. The early fly embryo is a fantastic model for understanding this event because of its ease of genetic manipulation and the large size of what is technically one cell. Abreu-Blanco and colleagues found that there are three phases in single-cell wound repair—brief expansion of the wound, contraction of the membrane, and closure of the wound. Images above show the accumulation of actin around a healing wound. Left column shows the surface of wound, while the right column shows a cross section.

BONUS!! Check out a movie of the image above here. Still want more movies from this paper? Click here.

Abreu-Blanco, M., Verboon, J., & Parkhurst, S. (2011). Cell wound repair in Drosophila occurs through three distinct phases of membrane and cytoskeletal remodeling originally published in The Journal of Cell Biology, 193 (3), 455-464 DOI: 10.1083/jcb.201011018

May 16, 2011

2011-05-16T07:00:00.003-04:00

No cell is an island. Cells are influenced by their environment around them, and migrating cells are especially receptive to the surface they are crawling over. Today’s image is from an elegant study on how different forces regulate cell shape and movement.

Cell migration is a highly coordinated process that depends on many factors. One of these factors is the cell’s adhesion to the underlying substrate, and a recent paper clearly spells out how the adhesion strength of a substrate directly affects a migrating cell’s shape and motility. In the images above, migrating cells were placed on surfaces of different adhesion strength. Cells crawling with either low or high adhesion are slow and round compared to cells crawling on surfaces with medium adhesion strength. These alterations in adhesion affect the localization of actin (top, red) and the actin motor myosin (middle, green).

Barnhart, E., Lee, K., Keren, K., Mogilner, A., & Theriot, J. (2011). An Adhesion-Dependent Switch between Mechanisms That Determine Motile Cell Shape PLoS Biology, 9 (5) DOI: 10.1371/journal.pbio.1001059

May 12, 2011

2011-05-12T07:00:00.003-04:00

Some of my favorite proteins ride on the ends of microtubules. I don’t usually like to anthropomorphize proteins, but I always think of Dr. Strangelove hopping on the growing end of a microtubule (and I didn’t even like that movie!). Today’s image is from a paper that adds a satisfying piece to the mitotic spindle puzzle.

Astrin is a mitotic spindle protein that is required for proper alignment of chromosomes on the metaphase plate during mitosis. It wasn’t clear exactly what astrin is doing to promote chromosome alignment, or how astrin arrives at the right location. A recent paper paints a much more complete astrin story. Dunsch and colleagues found a novel protein called kinastrin that forms a complex with astrin and a few others. Astrin localizes to the plus ends of microtubules, and requires kinastrin to do so. The presence of this complex may be affecting microtubule dynamics directly, consistent with the chromosome alignment and spindle integrity problems seen in kinastrin- and astrin-depleted cells. Image above shows fluorescently-tagged astrin localized to the ends of microtubules. The different colors show the localization of astrin in subsequent time-lapse images (ie, the astrin moves with the end of the microtubule).

Dunsch, A., Linnane, E., Barr, F., & Gruneberg, U. (2011). The astrin-kinastrin/SKAP complex localizes to microtubule plus ends and facilitates chromosome alignment originally published in The Journal of Cell Biology, 192 (6), 959-968 DOI: 10.1083/jcb.201008023

May 9, 2011

2011-05-09T07:00:00.003-04:00

“HELLO, my name is…tuft cell.” I’m sure a lot of folks wish that cells wore name tags to help identify them. In a sense, however, cells do wear name tags…we just have to figure out how to read them. A recent paper describes how to identify tuft cells in intestinal tissue, where they come from, and what jobs they perform.

Tuft cells are found in the intestinal epithelium, a tissue that is very dynamic and busy digesting food. Although tuft cells were identified in 1956, their origin, markers, and function remained unclear until recently. A group of researchers were recently able to identify markers that clearly define tuft cells within intestinal tissue. In addition, these biologists found that these cells come from a group of intestinal stem cells and function as secretory cells. In mice, tuft cells appear shortly after birth, as seen in the images above. Prior to birth (top), tuft cells are not found in the intestinal epithelium. However, after birth (middle, bottom), tuft cells can be detected by staining for DCLK1 (red, arrowheads), the tuft cell marker identified in the paper.

Gerbe, F., van Es, J., Makrini, L., Brulin, B., Mellitzer, G., Robine, S., Romagnolo, B., Shroyer, N., Bourgaux, J., Pignodel, C., Clevers, H., & Jay, P. (2011). Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium originally published in The Journal of Cell Biology, 192 (5), 767-780 DOI: 10.1083/jcb.201010127

May 5, 2011

2011-05-05T07:00:00.001-04:00

So much depends on healthy cell division, so it is no wonder how magnificent the spindle checkpoint is. This checkpoint keeps our cells healthy and our biologists busy as they try to figure it all out.

The spindle checkpoint ensures that a dividing cell undergoes anaphase only when all chromosomes are properly attached the mitotic spindle. Without this checkpoint, cells may end up with an incorrect number of chromosomes. Recently, a group teased apart some of the specifics of the checkpoint by using a construct engineered in the lab. This construct fused the kinetochore protein Mis12 to the checkpoint protein Mad1, which blocks progression to anaphase when it localizes to kinetochores not attached to the spindle. This Mad1-Mis12 construct targeted Mad1 to kinetochores despite their orientation state on the mitotic spindle, meaning that this construct allowed researchers to distinguish between Mad1 checkpoint signaling and the initial orientation error signal. The images above show metaphase spindles in control cells (top) or cells with the Mad1-Mis12 construct (bottom). The construct (mCherry, red in merged image) localizes to kinetochores (CREST, blue in merged) attached to the spindle (tubulin, green).

Maldonado, M., & Kapoor, T. (2011). Constitutive Mad1 targeting to kinetochores uncouples checkpoint signalling from chromosome biorientation Nature Cell Biology, 13 (4), 475-482 DOI: 10.1038/ncb2223
Adapted by permission from Macmillan Publishers Ltd, copyright 2011