1. Cell Biology
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The RhoGAP activity of CYK-4/MgcRacGAP functions non-canonically by promoting RhoA activation during cytokinesis

  1. Donglei Zhang
  2. Michael Glotzer  Is a corresponding author
  1. University of Chicago, United States
Research Article
  • Cited 39
  • Views 2,702
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Cite this article as: eLife 2015;4:e08898 doi: 10.7554/eLife.08898

Abstract

Cytokinesis requires activation of the GTPase RhoA. ECT-2, the exchange factor responsible for RhoA activation, is regulated to ensure spatiotemporal control of contractile ring assembly. Centralspindlin, composed of the Rho family GTPase-activating protein (RhoGAP) MgcRacGAP/CYK-4 and the kinesin MKLP1/ZEN-4, is known to activate ECT-2, but the underlying mechanism is not understood. We report that ECT-2-mediated RhoA activation depends on the ability of CYK-4 to localize to the plasma membrane, bind RhoA, and promote GTP hydrolysis by RhoA. Defects resulting from loss of CYK-4 RhoGAP activity can be rescued by activating mutations in ECT-2 or depletion of RGA-3/4, which functions as a conventional RhoGAP for RhoA. Consistent with CYK-4 RhoGAP activity contributing to GEF activation, the catalytic domains of CYK-4 and ECT-2 directly interact. Thus, counterintuitively, CYK-4 RhoGAP activity promotes RhoA activation. We propose that the most active form of the cytokinetic RhoGEF involves complex formation between ECT-2, centralspindlin and RhoA.

Article and author information

Author details

  1. Donglei Zhang

    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Michael Glotzer

    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States
    For correspondence
    mglotzer@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Mohan Balasubramanian, University of Warwick, United Kingdom

Publication history

  1. Received: May 21, 2015
  2. Accepted: August 6, 2015
  3. Accepted Manuscript published: August 7, 2015 (version 1)
  4. Version of Record published: September 1, 2015 (version 2)

Copyright

© 2015, Zhang & Glotzer

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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