title: A conserved RhoGAP limits M phase contractility and coordinates with microtubule asters to confine RhoA during cytokinesis.
abstract: During animal cell cytokinesis, the spindle directs contractile ring assembly by activating RhoA in a narrow equatorial zone. Rapid GTPase activating protein (GAP)-mediated inactivation (RhoA flux) is proposed to limit RhoA zone dimensions. Testing the significance of RhoA flux has been hampered by the fact that the GAP targeting RhoA is not known. Here, we identify M phase GAP (MP-GAP) as the primary GAP targeting RhoA during mitosis and cytokinesis. MP-GAP inhibition caused excessive RhoA activation in M phase, leading to the uncontrolled formation of large cortical protrusions and late cytokinesis failure. RhoA zone width was broadened by attenuation of the centrosomal asters but was not affected by MP-GAP inhibition alone. Simultaneous aster attenuation and MP-GAP inhibition led to RhoA accumulation around the entire cell periphery. These results identify the major GAP restraining RhoA during cell division and delineate the relative contributions of RhoA flux and centrosomal asters in controlling RhoA zone dimensions.
authors.affiliation: Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA; Center for Integrated Protein Science CIPSM, Department Biology II, Ludwig-Maximilians University, Munich, 82152 Planegg-Martinsried, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Zanin
authors.forename: Arshad
authors.initials: A
authors.lastname: Desai
authors.forename: Ina
authors.initials: I
authors.lastname: Poser
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Toyoda
authors.forename: Cordula
authors.initials: C
authors.lastname: Andree
authors.forename: Claudia
authors.initials: C
authors.lastname: Moebius
authors.forename: Marc
authors.initials: M
authors.lastname: Bickle
authors.forename: Barbara
authors.initials: B
authors.lastname: Conradt
authors.forename: Alisa
authors.initials: A
authors.lastname: Piekny
authors.forename: Karen
authors.initials: K
authors.lastname: Oegema
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D002455:Cell Division / Q000235:genetics; D048749:Cytokinesis / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D008870:Microtubules / Q000235:genetics; D008938:Mitosis / Q000235:genetics*; D009119:Muscle Contraction / Q000235:genetics; D020742:rhoA GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; C085379:rho GTPase-activating protein; D020742:rhoA GTP-Binding Protein