Dissecting Temporal and Spatial Control of Cytokinesis with a Myosin II Inhibitor

Science 299:1743 (2003/03)
Aaron Straight @ HMS

Microtubule associated with the mitotic apparatus plays an important role in cleavage furrow positioning has been known for a very long time since Rappaport’s elegant experiments. However, the real signals used to communicate between microtubules and cleavage furrow are largely unknown. By the help of ICCB in HMS, Aaron, then a postdoc in Tim Mitchison's lab and now a professor in Stanford, used the myosin II ATPase inhibitor Blebbistatin accompanying with other small molecules to study these questions.

This is a descriptive paper and some important findings were addressed in it. MG132 (100 uM) more than doubles the duration of C phase. It is an important finding because even till now no one really knows what determines the duration of C phase which is roughly ~50 minutes long after checkpoint inactivation.

Besides, nocodazole delocalized both myosin II and anillin. Latrunculin subtly disorganized microtubules and dislocated myosin II and anillin. Aaron concluded that communication from microtubules to the cortex is primary unidirectional. For this conclusion, I have doubt on it. In other systems, perturbation of actin cytoskeleton was reported to cause loss of midzone microtubules. And I have similar finding in my own results.

Applications of several kinase inhibitors such as staurosporine, Aurora-I, or Y27632 all delocalized myosin II but had no effect on anillin, suggesting anillin and myosin II are both actin dependent but regulated by two different mechanisms.
This paper is a old paper published on 2003. But it proved that at least for cytokinesis which happens extremely fast within a limited C phase window, small molecule is very useful of fast-acting and reversible drugs in such a dynamic cellular pathway.