Inhibition of Rac by the GAP activity of Centralspindlin is Essential for Cytokinesis

摘要

During cytokinesis, the small 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 GAP CYK-4, is required for central spindle assembly and cytokinesis. However, the importance of the CYK-4 GAP activity and whether it regulates RhoA remains unclear. Here, we show that two separation-of-function mutations in the GAP domain of C. elegans CYK-4 lead to cytokinesis defects that mimic Centralspindlin loss-of-function. These defects can be rescued by depletion of Rac or its effectors, but not RhoA. Our findings suggest that inactivation of Rac by Centralspindlin functions in parallel with RhoA activation to drive cytokinesis.