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
Reviewing Editor
- Mohan Balasubramanian, University of Warwick, United Kingdom
Publication history
- Received: May 21, 2015
- Accepted: August 6, 2015
- Accepted Manuscript published: August 7, 2015 (version 1)
- 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.
Metrics
-
- 2,702
- Page views
-
- 622
- Downloads
-
- 39
- Citations
Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.