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
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
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
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
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.
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
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
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
