Cytokinesis — the final stage in eukaryotic cell division — is achieved by the constriction of an actomyosin-based contractile ring and its associated plasma membrane, partitioning the cytoplasm into the daughter cells. The process is complete within a few minutes and is tightly regulated in space and time, but the exact mechanisms by which the cell cycle machinery regulates the contractile ring and the microtubules associated with the mitotic apparatus has been unclear. In the March 14 Science, Aaron Straight and colleagues at the Harvard Medical School, Boston, US, reported the discovery of a compound called blebbistatin that holds significant promise as a tool to understand how cytokinesis is regulated (Science, 299:1743-1747, March 14, 2003).

Straight et al. investigated the signals used in mammalian cells to communicate between the microtubule cytoskeleton, the actin cytoskeleton and the cell membrane, to identify a molecule that could inhibit contraction of the cleavage ring without disrupting assembly of the ring itself or mitosis. They used a high throughput method to screen a small-molecule library for inhibitors of nonmuscle myosin II — a protein crucial for contraction of the cleavage ring — and identified blebbistatin. The compound specifically blocked all myosin II-dependent processes in vertebrate cells, including cytokinesis and cell blebbing.

Using blebbistatin and other drugs, Straight et al. showed that ubiquitin-mediated proteolysis is required to exit mitosis in mammalian cells, confirming earlier observations in yeast. They also determined that a complex network of signaling from microtubules to the cell membrane is necessary to establish the cleavage ring and to maintain its proper localization during cell division.

"Our experiments emphasize the usefulness of fast-acting and reversible drugs in a dynamic cellular pathway such as cytokinesis," conclude the authors.