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 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