March 22, 2012

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

January 19, 2012

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

October 31, 2011

All storytellers want to tell their story all the way to its end. Imagine how unsatisfying most movies or books would be without their endings. What if Scout didn’t get to meet Boo Radley? How boring would The Sixth Sense be? How tragic would Toy Story 3 be?! In cell biology, telling a whole story in one paper, from protein to cell to animal, is a rare luxury given the time and difficulty of most techniques. Today’s image is from a paper with a well-rounded story about the role of a cell cycle protein in non-cell cycle-related business.

The cell cycle is driven forward by complexes made up of proteins called cyclins and cyclin-dependent kinases (Cdks). One cyclin called cyclin E functions in the G1 to S phase transition in the cell cycle, marking the start of DNA replication. Because of this role, cyclin E is typically found in only dividing cells. A recent paper describes the important role of cyclin E in non-dividing cells in the adult brain. In this paper, Odajima and colleagues found that cyclin E regulates synapse formation by inhibiting Cdk5. Cyclin E disruption in neurons causes the number of synapses and dendritic spines to drop. Finally, adult mice with cyclin E-deficient brains had impaired learning and memory. In the images above, non-dividing neurons from mouse brain show the presence of cyclin E (red) in both axons and dendrites, along with Cdk5. SynGAP and Synapsin I are post- and presynaptic markers.

Odajima, J., Wills, Z., Ndassa, Y., Terunuma, M., Kretschmannova, K., Deeb, T., Geng, Y., Gawrzak, S., Quadros, I., Newman, J., Das, M., Jecrois, M., Yu, Q., Li, N., Bienvenu, F., Moss, S., Greenberg, M., Marto, J., & Sicinski, P. (2011). Cyclin E Constrains Cdk5 Activity to Regulate Synaptic Plasticity and Memory Formation Developmental Cell, 21 (4), 655-668 DOI: 10.1016/j.devcel.2011.08.009
Copyright ©2011 Elsevier Ltd. All rights reserved.

January 24, 2011

When we first learned about the cell cycle in high school, we learned about the stunning simplicity of certain proteins that cycle in order to promote progression through the cell cycle. In reality, that picture is quite complex, with many layers of regulation that affect those cycling proteins. A recent paper from the Nurse lab pares down all of that complexity to show us that the simplicity really has been there all along.

The cell cycle is the sequence of events that leads to a cell’s division and is regulated by two classes of molecules – cyclins and cyclin-dependent kinases (CDKs). Progression through the cell cycle is an orderly process, yet the integration of all players involved is complex—different CDKs associate with different cyclins, which are synthesized and degraded at different times, and these associations are regulated by their localization, interaction with inhibitors, checkpoint mechanisms, and complex feedback loops. A recent paper shows that a single cyclin-CDK “engine” is the core mechanism driving cell cycle progression in fission yeast. Coudreuse and Nurse show that without all of the regulatory inputs and feedback loops, a single engineered module containing Cdc2 (a CDK) and Cdc13 (cyclin B) is sufficient to drive cell division. Image above is of a fission yeast cell going through the cell cycle with this engineered module – top row shows the appearance and degradation of the engineered module, while the bottom row shows the DNA.

Adapted by permission from Macmillan Publishers Ltd, copyright 2010.

Coudreuse, D., & Nurse, P. (2010). Driving the cell cycle with a minimal CDK control network Nature, 468 (7327), 1074-1079 DOI: 10.1038/nature09543