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

American Association for the Advancement of Science (AAAS) - Tập 299 Số 5613 - Trang 1743-1747 - 2003
Aaron F. Straight1, Amy Cheung1, John Limouze2, Irene A. Chen3, Nicholas J. Westwood4, James R. Sellers2, Timothy J. Mitchison1
1Department of Cell Biology and Institute of Chemistry and Cell Biology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
2Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health Bethesda, MD 20892, USA
3Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 USA
4School of Chemistry, University of St. Andrews, St. Andrews, Fife KY16 9AJ, UK

Tóm tắt

Completion of cell division during cytokinesis requires temporally and spatially regulated communication from the microtubule cytoskeleton to the actin cytoskeleton and the cell membrane. We identified a specific inhibitor of nonmuscle myosin II, blebbistatin, that inhibited contraction of the cleavage furrow without disrupting mitosis or contractile ring assembly. Using blebbistatin and other drugs, we showed that exit from the cytokinetic phase of the cell cycle depends on ubiquitin-mediated proteolysis. Continuous signals from microtubules are required to maintain the position of the cleavage furrow, and these signals control the localization of myosin II independently of other furrow components.

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We thank E. M. Ostap for purified myosin Ib; J. Dantzig A. Shaw and Y. M. Goldman for rabbit skeletal myosin SI; L. Flanagan and T. Stossel for M2 cells; K. Pierce and M. M.-C. Lofor assistance with chiral chromatography; S. Miller and T. Kapoor for advice on chemical synthesis; T. Kapoor for assistance with aurora kinase inhibitors; and A. Farrell W. Brieher and R. Ward for stimulating discussion and critical review of the manuscript. This work was supported by grants from the NIH (GM62566 GM23928) to T.J.M. and from Merck & Co. and E. Merck. A.F.S. was supported by the Cancer Research Fund of the Damon Runyon–Walter Winchell Foundation.

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American Association for the Advancement of Science (AAAS)

Tập 299 Số 5613

1743-1747

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