July 17, 2013

We don’t need to reinvent the wheel (even if someone tried to in 2001...click here).  We use the wheel for so many things ranging from transport to energy.  Cells have proven clever at co-opting machinery for multiple processes, as the paper from today’s image describes.  This recent paper shows the use of specific machinery in both cytokinesis and neuronal migration.

When neurons migrate, there is a leading process in the front of the cell body and a trailing process.  The leading process contains actin filaments that enable the cell body of the neuron to move forward.  A recent paper describes how the microtubule-based motor kinesin-6 plays an important role in neuronal migration.  Kinesin-6 is best known for its role in cytokinesis, the physical division of a cell after mitosis.  Falnikar and colleagues found that kinesin-6 concentrates in the same region as actin filaments in the leading process of a migrating neuron.  Without kinesin-6, neurons lose their bipolar leading-trailing process morphology, concentrate actin filaments in more than one process, and either remain stationary or continually change the direction of migration.  In addition, Falnikar and colleagues found that kinesin-6 signals through the GTPase activating protein MgcRacGAP to regulate the actin cytoskeleton, as it does during cytokinesis.  In the images above, control neurons (top time-lapse series) moved in a single direction, while neurons depleted of kinesin-6 bottom) frequently changed directions.

BONUS!!  Check out a movie of a wandering, migrating kinesin-6-depleted neuron below.

Aditi Falnikar, Shubha Tole, Mei Liu, Judy S. Liu, & Peter W. Baas (2013). Polarity in Migrating Neurons Is Related to a Mechanism Analogous to Cytokinesis Current Biology, 23 (13), 1215-1220 DOI: 10.1016/j.cub.2013.05.027 Copyright ©2013 Elsevier Ltd. All rights reserved.

March 26, 2012

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

February 27, 2012

Yeast is magical. It gives our bread and beer its deliciousness, and provides biologists with a fantastic tool for understanding cell biology. Many of our monumental cell biology discoveries were due to yeast, so please whisper a heartfelt “Thank you” to yeast the next time you enjoy a beer. Today’s image is from a paper describing the structure of the septin network required for cell division in yeast.

Many yeast species divide by budding – a mother cell replicates its genome within its nucleus while a small bud forms and grows. The nucleus divides and the bud splits off of the mother cell. This split between mother and bud, or cytokinesis, depends on structural proteins called septins. Although the structure and function of septins has been studied for years, exactly how they are arranged at the bud neck of dividing yeast was not clear. Despite the small size of the bud neck, Bertin and colleagues recently imaged septin ultrastructure in dividing yeast cells by using improved techniques of electron microscopy that allow better preservation of membranes, combined with three-dimensional reconstruction of images. Specifically, Bertin and colleagues found septin filaments that ran both parallel and perpendicular to the mother-bud axis. In the images above, a view of the bud neck near the top of the membrane (top) shows circumferential filaments (green arrows). In a deeper view of the bud neck (bottom), filaments that follow the contour of the bud neck (next to red lines) can be seen, as well as a cross-sectional view of the circumferential filaments (green arrows).

Bertin, A., McMurray, M., Pierson, J., Thai, L., McDonald, K., Zehr, E., Garcia, G., Peters, P., Thorner, J., & Nogales, E. (2011). Three-dimensional ultrastructure of the septin filament network in Saccharomyces cerevisiae Molecular Biology of the Cell, 23 (3), 423-432 DOI: 10.1091/mbc.E11-10-0850

February 2, 2012

When a cell makes it all the way to cytokinesis, it has already achieved greatness. DNA replication and mitosis are Big Deals, but a cell exits mitosis only to find itself in front of that final all-uphill mile of the New York City Marathon (even as a kid watching it, I thought that was so cruel). There is a lot of regulation and reorganizing that happens for a cell to correctly complete cell division and physically split into two cells, and a recent paper sorts out how membrane trafficking proteins are coordinated during the process.

Cytokinesis is the final step of cell division, when the two daughter cells are physically divided. At the start of cytokinesis, a contractile ring forms around the center of the dividing cell and begins to tighten. These contractions result in a cleavage furrow forming and pinching the dividing cell, after which only an intercellular bridge connects the two new daughter cells. With all of this contracting and pinching of the plasma membrane, it is no surprise that membrane trafficking proteins are important during cytokinesis. A recent paper looks at how endocytosis and membrane trafficking pathways are coordinated during cytokinesis. Specifically, Chesneau and colleagues found that Rab35 GTPase, an endocytic protein known to also be important in cytokinesis, is negatively regulated by ARF GTPase. ARF mutants (ones that are stuck in the activated GTP state, for those paying attention) have cytokinesis defects similar to Rab35 mutants (stuck in the inactive GDP state), including a failure after cleavage furrow progression and an instability of intercellular bridges. A seen in the images above, both the ARF mutant (bottom) and Rab35 mutant (middle) mislocalize a protein called SEPTIN2 (green, arrowheads), which is a cytoskeletal element that provides structure during cytokinesis. In a normal cell (top), SEPTIN2 is localized at the cleavage furrow.

Chesneau, L., Dambournet, D., Machicoane, M., Kouranti, I., Fukuda, M., Goud, B., & Echard, A. (2012). An ARF6/Rab35 GTPase Cascade for Endocytic Recycling and Successful Cytokinesis Current Biology DOI: 10.1016/j.cub.2011.11.058

Copyright ©2011 Elsevier Ltd. All rights reserved.

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).

Gai, 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

March 24, 2011

Cancer cells have taught biologists about a lot of wacky things that can happen when things don’t go merrily along for a cell. Entosis is a process in which a living cell is internalized into a neighboring cell, and has been found to occur in some tumors. A recent paper describes exactly what can go wrong here.

Aneuploidy refers to a cell having an incorrect number of chromosomes, and is a feature of many cancers. Typically, aneuploidy occurs from a failure in cytokinesis, the physical division of a cell after mitosis, due to misregulation or mutation of genes involved in cell division. Sometimes, however, aneuploidy can occur from a non-genetic failure of cytokinesis, according to a recent paper. In this paper, Krajcovic and colleagues look at cytokinesis failures due to entosis, a process in which living cells are internalized by their neighboring cells. These cell-in-cell structures are found in some tumors, and the outer “host” cell is frequently aneuploid. This aneuploidy occurs when the internalized cell physically disrupts the constriction required to cleave two cells during cytokinesis, as seen in the images above. Cytokinesis of the cell-in-cell structure (left) is not going well compared with a normal cell (right). Red labels (and in black and white insets) mark active constriction during cytokinesis, and should be symmetric around the cells. The mitotic spindle is labeled in green, and chromosomes in blue.

BONUS!! Movie of above cell, attempting cytokinesis, can be found here. More cool movies from this paper can be found here.

Krajcovic, M., Johnson, N., Sun, Q., Normand, G., Hoover, N., Yao, E., Richardson, A., King, R., Cibas, E., Schnitt, S., Brugge, J., & Overholtzer, M. (2011). A non-genetic route to aneuploidy in human cancers Nature Cell Biology, 13 (3), 324-330 DOI: 10.1038/ncb2174
Adapted by permission from Macmillan Publishers Ltd, copyright 2011

October 7, 2010

There are a few processes in a cell that simply blow my mind as I try to grasp how such a complex task is accomplished correctly every time. Cytokinesis is one of them, and is an absolutely elegant process to watch.

Cytokinesis is the step during cell division that physically splits a cell in half. Cytokinesis depends on actin, myosin, and many regulatory proteins, and a recent paper helps sort out where and how these proteins interact. Image above shows two cells undergoing cytokinesis, with microtubules remaining from the mitotic spindle (red), chromosomes (blue), and an actin-nucleating factor called mDia2 (green). The control cell (top) shows mDia2 localization at the cleavage furrow, the indentation of membrane at the beginning of cytokinesis; however, without a protein that regulates an mDia2 activator, mDia2 levels are reduced at the cleavage furrow.

Reference: Sadanori Watanabe, Katsuya Okawa, Takashi Miki, Satoko Sakamoto, Tomoko Morinaga, Kohei Segawa, Takatoshi Arakawa, Makoto Kinoshita, Toshimasa Ishizaki, and Shuh Narumiya. Authors’ Molecular Biology of the Cell paper can be found here.

July 15, 2010

The different sub-populations of microtubules of the mitotic spindle play different roles. Astral microtubules interact with the cell cortex, and this contact is important for regulating the position of the cleavage furrow that begins cytokinesis, the splitting of the cell into two daughter cells. A recent paper shows that after treatment to elongate astral microtubules, the mitotic spindle rocked severely. This rocking is due to a change in the location of the actin cytoskeleton at the cortex prior to cytokinesis. Image above shows mitotic cells with (right) or without (left) the treatment to elongate astral microtubules, and higher magnified regions underneath.

Reference: Kathleen E. Rankin and Linda Wordeman, 2010. Originally published in Journal of Cell Bioloy. doi: 10.1083/jcb.201004017. Paper can be found here. Check out the authors’ cover image for the same issue of JCB here.

June 3, 2010

Cytokinesis is the division of a cell’s cytoplasmic contents after mitosis. This complex process depends on many proteins that regulate the contractile ring, which constricts until the two new daughter cells are completely separate. A recent paper has looked into the mechanisms of the contractile ring in spermatocytes in the fruit fly Drosophila. The authors found that cytokinesis can be completed by two different complexes of proteins that stabilize actin and myosin at the contractile ring—an anillin-septin complex and a cadherin-catenin complex. Image of spermatocytes above shows colocalization of actin(red) and anillin(green) at sites of cytokinesis (arrows).

Reference: Philip Goldbach, Raymond Wong, Nolan Beise, Ritu Sarpal, William S. Trimble, and Julie A. Brill. Authors’ Molecular Biology of the Cell paper can be found here.