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Science 5 December 2008:
Vol. 322. no. 5907, pp. 1543 - 1546
DOI: 10.1126/science.1163086
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Reports

Inhibition of Rac by the GAP Activity of Centralspindlin Is Essential for Cytokinesis

Julie C. Canman,1,2* Lindsay Lewellyn,2 Kimberley Laband,2 Stephen J. Smerdon,3 Arshad Desai,2 Bruce Bowerman,1{dagger} Karen Oegema2*{dagger}

During cytokinesis, the guanosine triphosphatase (GTPase) RhoA orchestrates contractile ring assembly and constriction. RhoA signaling is controlled by the central spindle, a set of microtubule bundles that forms between the separating chromosomes. Centralspindlin, a protein complex consisting of the kinesin-6 ZEN-4 and the Rho family GTPase activating protein (GAP) CYK-4, is required for central spindle assembly and cytokinesis in Caenorhabditis elegans. However, the importance of the CYK-4 GAP activity and whether it regulates RhoA remain unclear. We found that two separation-of-function mutations in the GAP domain of CYK-4 lead to cytokinesis defects that mimic centralspindlin loss of function. These defects could be rescued by depletion of the GTPase Rac or its effectors, but not by depletion of RhoA. Thus, inactivation of Rac by centralspindlin functions in parallel with RhoA activation to drive contractile ring constriction during cytokinesis.

1 Institute for Molecular Biology, University of Oregon, Eugene, OR 97403, USA.
2 Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
3 National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.

{dagger} These authors contributed equally to this work.

* To whom correspondence should be addressed. E-mail: jcanman{at}ucsd.edu (J.C.C.); koegema{at}ucsd.edu (K.O.)

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Science. ISSN 0036-8075 (print), 1095-9203 (online)