MgcRacGAP controls the assembly of the contractile ring and the initiation of cytokinesis.
Initiation of cytokinesis requires the establishment of the cleavage plane, the assembly of the contractile ring, and the ingression of the cleavage furrow. MgcRacGAP, a GTPase-activating protein for RhoA, is required for cytokinesis, but the mechanism of its action remains unknown. We report here that MgcRacGAP is required for the assembly of anillin and myosin into the contractile ring. In addition, MgcRacGAP is required for the localized activation of myosin through the RhoA-mediated phosphorylation of the myosin regulatory light chain. Cells with MgcRacGAP RNA interference (RNAi) failed cytokinesis without any ingression of the cleavage furrow. Paradoxically, MgcRacGAP, a GTPase-activating protein, associates during cytokinesis with ECT2, a guanine nucleotide exchange factor for RhoA, and the localization of ECT2 to both the central spindle and the contractile ring depends on MgcRacGAP. Knockdown of ECT2 phenocopies that of MgcRacGAP. We conclude that MgcRacGAP controls the initiation of cytokinesis by regulating ECT2, which in turn induces the assembly of the contractile ring and triggers the ingression of the cleavage furrow.
Zhao
Wei-meng
WM
Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA.
Fang
Guowei
G
D003285:Contractile Proteins / Q000378:metabolism; D048749:Cytokinesis; D003599:Cytoskeleton / Q000378:metabolism* / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D018994:Myosin Light Chains / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D008941:Spindle Apparatus / Q000378:metabolism; D014162:Transfection; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D003285:Contractile Proteins; C489850:ECT2 protein, human; D020690:GTPase-Activating Proteins; D018994:Myosin Light Chains; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; C095886:anillin; C115995:mgcRacGAP; C066737:RHOA protein, human; D009218:Myosins; D020742:rhoA GTP-Binding Protein