Happy Holidays!

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

December 19, 2011

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.


ResearchBlogging.orgMeunier, 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

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.

ResearchBlogging.orgGong, 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


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.

ResearchBlogging.orgJohnson, 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

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

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%.

ResearchBlogging.orgHayakawa, 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

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.

ResearchBlogging.orgBharat, 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

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).

ResearchBlogging.orgCarmena, 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!

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

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.

ResearchBlogging.orgKrementsova, 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

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).

ResearchBlogging.orgGeiger, 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

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.

ResearchBlogging.orgMarshall, 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

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).

ResearchBlogging.orgJoyce, 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

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.

ResearchBlogging.orgStephan, 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

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.

ResearchBlogging.orgYi, 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


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.


ResearchBlogging.orgOdajima, 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

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-xL. A recent paper finds a new, non-apoptosis role for Bcl-xL 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-xL is a Bcl-2 family member that inhibits apoptosis by binding Bax, a pro-apoptosis family member, at the outer membrane of mitochondria. There, Bcl-xL 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-xL outside of apoptosis. Chen and colleagues found Bcl-xL localized to the inner mitochondrial membrane, contrary to previous opinion that it is only found at the outer mitochondrial membrane. At the inner membrane, Bcl-xL is 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-xL are 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).

ResearchBlogging.orgChen, 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

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).

ResearchBlogging.orgGai, 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

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).

ResearchBlogging.orgBrill, 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

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.

ResearchBlogging.orgTammela, 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

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).

ResearchBlogging.orgFriedrich 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

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.


ResearchBlogging.orgLippi, 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