“Hang in there!” says the kitten dangling from a tree branch. Maybe this poster from my junior high-era bedroom should have had a white blood cell instead. While defending the body from infection, white blood cells have to anchor themselves to avoid being swept away from the constant blood flow around them. Today’s image is from a recent paper showing how this happens.
Leukocytes, or white blood cells, find their way to sites of infection in the body. Once there, leukocytes are subjected to the force of blood flow around them and must resist detachment from the inflamed tissue. Integrin cell adhesion proteins are important in stabilizing the anchors formed on leukocytes recruited to inflamed tissue. A recent paper shows that rapid actin polymerization at adhesion sites is triggered by the force of blood flow. In addition, Rullo and colleagues show that this actin polymerization is necessary for successful attachment. Image above shows human leukocytes on a surface coated with VCAM-1, a leukocyte adhesion molecule, and exposed to a fluid flow in the direction of the arrow. Arrowhead points to anchor points.
Rullo, J., Becker, H., Hyduk, S., Wong, J., Digby, G., Arora, P., Cano, A., Hartwig, J., McCulloch, C., & Cybulsky, M. (2012). Actin polymerization stabilizes 4 1 integrin anchors that mediate monocyte adhesion originally published in the Journal of Cell Biology, 197 (1), 115-129 DOI: 10.1083/jcb.201107140
Membranes really know how to mingle. They are dynamic in the cell—budding away from one organelle to fuse with another, remodeling themselves for the situation. My awkward party persona should take some notes…I’ve never seen membranes hang out next to the Chex Mix bowl all night. Today’s image is from a recent paper on membrane scission and the role of membrane remodeling proteins.
The membranes that compartmentalize a cell’s organelles are under constant transformation. Membrane sculpting is a coordinated process that includes bending membranes and remodeling by fission and fusion (severing and joining, respectively). Membrane curvature is introduced two different ways—by hydrophobic insertions into the membrane’s lipid bilayer, or by the presence of a scaffold made of curved BAR domain proteins. A recent paper sheds light on how these two membrane-remodeling mechanisms affects membrane fission. According to Boucrot and colleagues, the membrane insertion of a protein called epsin, which contains a hydrophobic ENTH domain, leads to membrane fission, while the curved BAR-domain scaffolds actually limit membrane fission. In addition, epsin is required for membrane fission of clathrin-coated vesicles. The electron micrograph above shows a clathrin-coated vesicle after depletion of all epsin proteins. Without epsin, vesicles are unable to bud from one another, creating a multi-headed structure.
Boucrot, E., Pick, A., Çamdere, G., Liska, N., Evergren, E., McMahon, H., & Kozlov, M. (2012). Membrane Fission Is Promoted by Insertion of Amphipathic Helices and Is Restricted by Crescent BAR Domains Cell, 149 (1), 124-136 DOI: 10.1016/j.cell.2012.01.047
Copyright ©2012 Elsevier Ltd. All rights reserved.
Sometimes I read something that elicits an old-school Joey Lawrence, “Whoa!” I may not be an early 90s heartthrob with voluminous hair, but sometimes the science world makes me sound like one. Today’s image is from a paper on emergence—not a particularly common topic in cell biology, but here the use of microtubules helps to model and test it.
Emergence describes the spontaneous order that can arise out of simple interactions of things. Examples of emergent phenomena in nature include flocks of birds, swarms of bees, ordered crystals of freezing water. The theories behind this collective behavior are tough to test due to the difficulty in controlling all variables and interactions. A recent paper, however, uses emergence at a cellular level to control for all interactions with only a few purified components. Here, Sumino and colleagues used purified microtubules propelled by dynein motors that were bound to a glass surface. Neighboring microtubules, which were on average 15um long, interacted by aligning with each other. Increased density of these local interactions resulted in the self-organization of microtubules into vortices about 400um in diameter, with microtubules rotating and sliding past each other in both clockwise and counter-clockwise directions. Image above shows a lattice formed from many vortices over time (three air bubbles are present with thicker edges).
BONUS! Check out movies from this paper here, under “Supplementary Information.” This one is my favorite!
Sumino, Y., Nagai, K., Shitaka, Y., Tanaka, D., Yoshikawa, K., Chaté, H., & Oiwa, K. (2012). Large-scale vortex lattice emerging from collectively moving microtubules Nature, 483 (7390), 448-452 DOI: 10.1038/nature10874
Adapted by permission from Macmillan Publishers Ltd, copyright ©2012
A good chunk of my personal pride is about my ability to wear several hats. I can cook a mean dinner, read that awesome new Myo10 paper, and fix a leaking faucet all while braiding my little girl’s hair and constructing a garden scene out of PlayDoh. So, today’s image makes me tip my many hats to Myo10 and its newly-recognized role in polarized cells.
Myo10 is a member of the giant family of myosin actin motors. Myo10 localizes to the tips of thin actin-rich membrane extensions, called filopodia, in non-polarized fibroblast-like cells and plays an important role in the formation and function of filopodia. A recent paper describes the role of Myo10 in a very different type of cell—the polarized epithelial cell. According to Liu and colleagues, Myo10 is important during formation of the cell-cell junctions that adhere epithelial cells together in a highly organized sheet. Myo10 is found at cell-cell contact points during junction formation, and helps ensure the timely localization of essential junction proteins. In addition, the leak-proof barrier function of an epithelial sheet is compromised in cells with reduced levels of Myo10. The images above show epithelial cysts, frequently used to model the three-dimensional formation of epithelial tissue in culture. Cysts with normal levels of Myo10 (top row) developed a single lumen, while cysts with reduced levels of Myo10 frequently had more than one lumen (bottom row), pointing to a role for Myo10 in epithelial morphogenesis. Junctional markers (ZO-1 is green, E-cadherin is red), however, are still properly localized in cysts with reduced Myo10.
Liu, K., Jacobs, D., Dunn, B., Fanning, A., & Cheney, R. (2012). Myosin-X Functions in Polarized Epithelial Cells Molecular Biology of the Cell DOI: 10.1091/mbc.E11-04-0358
I think polar bodies are pretty cute. These little nubbins are products of meiotic division, and a simple testament to how amazing and clever a dividing cell (an oocyte, in this case) can be. Sure, polar bodies aren’t around for long, but I thank my own two long-lost polar bodies that let me have enough nutrients to survive. I hardly knew you, Atticus and Grover. Today’s image is from a paper describing anaphase in mouse oocyte divisions.
Meiosis is a special type of cell division that produces eggs and sperm. In mice, the meiotic spindle in the developing egg, or oocyte, is small and positioned in a very asymmetric location. This helps ensure that the nutrient- and organelle-rich cytoplasm stays with the daughter cell (the egg) that will later be fertilized and support early embryonic development. The other daughter of the division is the polar body, a small round structure that eventually is degraded. A recent paper describes results showing the sequence of anaphase events during mouse meiosis. In most cases of cell division, chromosome separation during anaphase is achieved by the shortening of kinetochore microtubules (termed anaphase A) and the lengthening of the entire meiotic spindle (anaphase B). In most cell divisions, anaphase A precedes anaphase B, yet Greg FitzHarris has shown that the reverse is true in mouse oocytes. Early anaphase B helps to determine the final size of the polar body. In addition, this early anaphase B spindle lengthening is triggered by the loss of tension on kinetochore microtubules, which occurs when cohesion between sister chromatids is lost. The images above are timepoints of anaphase in a mouse oocyte, with microtubules (grey) and chromosomes (green) labeled.
FitzHarris, G. (2012). Anaphase B Precedes Anaphase A in the Mouse Egg Current Biology, 22 (5), 437-444 DOI: 10.1016/j.cub.2012.01.041
Copyright ©2012 Elsevier Ltd. All rights reserved.
In a talk about midbodies while I was in graduate school, a fellow worm biologist* once endearingly described the midbody as a little “turd”. This talk signaled to me that 1) midbodies are totally fascinating, and 2) I can still have my third-grader sense of humor, giggle at the word “turd” AND be a biologist at the same time. Today’s stunning image is from a paper describing a thorough analysis of midbody assembly and maturation.
At the end of cytokinesis, the two resulting daughter cells are separated at the site of the midbody. This structure is derived from the midzone, which is a zone of overlapping microtubules that assembles between the separating chromosomes during anaphase. The midbody is made of this microtubule bundle as well as proteins involved in cytoskeletal regulation and membrane trafficking, and is very compact. In fact, the center of the midbody is so tightly packed that antibodies cannot reach the proteins, in turn preventing immunofluorescent imaging. A recent paper describes how known midbody proteins are rearranged and regulated as the structure assembles and matures. Hu and colleagues found that the proteins from the midzone/midbody fall into three different subgroups that localize to different regions, each subgroup likely having a different function in the mature midbody. In the images above, the proteins CENPE (red) and RacGAP1 (blue) colocalize at the midzone during anaphase (left). After that, the localization of the proteins changes (middle, left)—CENPE flanks RacGAP1 at midbodies starting from furrow ingression in cytokinesis.
*Guesses?
Hu, C., Coughlin, M., & Mitchison, T. (2012). Midbody assembly and its regulation during cytokinesis Molecular Biology of the Cell, 23 (6), 1024-1034 DOI: 10.1091/mbc.E11-08-0721
I love mitotic spindles, so of course I love early fruit fly development and its rapid, synchronized syncytial divisions. Watching these mitotic spindles perform a synchronized swimming routine, complete with tiny little swim caps and nose plugs, is always a treat. Today’s image is from a paper that helps to define the relationship between DNA replication, chromosome condensation, and mitotic progression.
During the cell cycle, DNA strands are replicated. After proper DNA replication, the very long strands are compacted in order to allow efficient and accurate separation of chromosomes during mitosis. When chromosome condensation doesn’t occur correctly, the progress through mitosis is disrupted. This may be due to the well-studied spindle assembly checkpoint, or there may be a checkpoint that monitors chromosome condensation. A recent paper describes results showing the effects of certain inhibitors on chromosome condensation and mitotic progression, marked by entry into anaphase. Fasulo and colleagues found that the inhibitors that severely disrupted chromosome condensation also disrupted anaphase onset. These delays occurred through disruption of the Wee1 kinase, and not due to the spindle assembly checkpoint. By using the early fruit fly embryo, Fasulo and colleagues could track many synchronized cell divisions at once, allowing for fast and direct analysis of the effects of the various inhibitors used. The cartoon and images above show the different steps during mitosis of these divisions. Both chromosomes (top row of images, green in merged) and microtubules (middle row of images, red in merged) are fluorescently tagged.
Fasulo, B., Koyama, C., Yu, K., Homola, E., Hsieh, T., Campbell, S., & Sullivan, W. (2012). Chk1 and Wee1 kinases coordinate DNA replication, chromosome condensation, and anaphase entry Molecular Biology of the Cell, 23 (6), 1047-1057 DOI: 10.1091/mbc.E11-10-0832
