title: Inhibition of Rac by the GAP activity of centralspindlin is essential for cytokinesis.
abstract: 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.
authors.affiliation: Institute for Molecular Biology, University of Oregon, Eugene, OR 97403, USA. jcanman@ucsd.edu
authors.forename: Julie C
authors.initials: JC
authors.lastname: Canman
authors.forename: Lindsay
authors.initials: L
authors.lastname: Lewellyn
authors.forename: Kimberley
authors.initials: K
authors.lastname: Laband
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Smerdon
authors.forename: Arshad
authors.initials: A
authors.lastname: Desai
authors.forename: Bruce
authors.initials: B
authors.lastname: Bowerman
authors.forename: Karen
authors.initials: K
authors.lastname: Oegema
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048749:Cytokinesis; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017238:Genes, Helminth; D016547:Kinesins / Q000378:metabolism; D009154:Mutation; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000502:physiology / Q000648:ultrastructure; D020744:rac GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000097766:RAC2 GTP-Binding Protein
chemical_list: D029742:Caenorhabditis elegans Proteins; D020690:GTPase-Activating Proteins; D016547:Kinesins; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein; C407268:CED-10 protein, C elegans; C513388:CYK-4 protein, C elegans; C114455:ZEN-4 protein, C elegans