Canman Julie C, Lewellyn Lindsay, Laband Kimberley, Smerdon Stephen J, Desai Arshad, Bowerman Bruce, Oegema Karen
Institute for Molecular Biology, University of Oregon, Eugene, OR 97403, USA.
Science. 2008 Dec 5;322(5907):1543-6. doi: 10.1126/science.1163086.
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.
在胞质分裂过程中，鸟苷三磷酸酶（GTPase）RhoA协调收缩环的组装和收缩。RhoA信号传导由中央纺锤体控制，中央纺锤体是一组在分离的染色体之间形成的微管束。中央纺锤体蛋白复合体由驱动蛋白-6 ZEN-4和Rho家族GTP酶激活蛋白（GAP）CYK-4组成，是秀丽隐杆线虫中央纺锤体组装和胞质分裂所必需的。然而，CYK-4的GAP活性的重要性以及它是否调节RhoA仍不清楚。我们发现CYK-4的GAP结构域中的两个功能分离突变导致了类似于中央纺锤体蛋白复合体功能丧失的胞质分裂缺陷。这些缺陷可以通过消耗GTP酶Rac或其效应器来挽救，但不能通过消耗RhoA来挽救。因此，中央纺锤体蛋白复合体使Rac失活与RhoA激活并行发挥作用，以在胞质分裂过程中驱动收缩环收缩。
