Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 5 December 2008:
Vol. 322. no. 5907, pp. 1543 - 1546
DOI: 10.1126/science.1163086
Prev | Table of Contents | Next

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.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Myosin II Recruitment during Cytokinesis Independent of Centralspindlin-mediated Phosphorylation.
J. R. Beach and T. T. Egelhoff (2009)
J. Biol. Chem. 284, 27377-27383
   Abstract »    Full Text »    PDF »
Proteomic Analysis of Integrin-Associated Complexes Identifies RCC2 as a Dual Regulator of Rac1 and Arf6.
J. D. Humphries, A. Byron, M. D. Bass, S. E. Craig, J. W. Pinney, D. Knight, and M. J. Humphries (2009)
Science Signaling 2, ra51
   Abstract »    Full Text »    PDF »
Dynamics of myosin, microtubules, and Kinesin-6 at the cortex during cytokinesis in Drosophila S2 cells.
R. D. Vale, J. A. Spudich, and E. R. Griffis (2009)
J. Cell Biol. 186, 727-738
   Abstract »    Full Text »    PDF »
Widely Conserved Signaling Pathways in the Establishment of Cell Polarity.
L. M. McCaffrey and I. G. Macara (2009)
Cold Spring Harb Perspect Biol 1, a001370
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

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