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
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
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
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
“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
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
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
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
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.
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
