title: Identification of a mitotic Rac-GEF, Trio, that counteracts MgcRacGAP function during cytokinesis.
abstract: The Rho GTPases RhoA and Rac1 function as master regulators of cytokinesis by controlling the actomyosin cytoskeleton. RhoA and Rac1 have to be respectively activated and inactivated at the division plane for cytokinesis to occur properly. The inactivation of Rac1 at the cleavage furrow is controlled by MgcRacGAP. However, the guanine-nucleotide exchange factor (GEF) that activates Rac1 during cell division remains unknown. Here, using a siRNA screening approach in HeLa cells, we identify Trio as a mitotic GEF of Rac1. We demonstrate that Trio controls Rac1 activation and subsequent F-actin remodeling in dividing cells. Moreover, Trio depletion specifically rescues the cytokinesis failure induced by MgcRacGAP depletion. Of importance, we demonstrate that this rescue is mediated by the Trio-Rac1 pathway, using GEF-dead mutants of Trio and a specific inhibitor of Rac1 activation by Trio. Overall this work identifies for the first time a GEF controlling Rac1 activation in dividing cells that counteracts MgcRacGAP function in cytokinesis.
authors.affiliation: Signaling and Cytoskeleton Dynamics Group, University of Montpellier, 34293 Montpellier, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Cannet
authors.affiliation: Signaling and Cytoskeleton Dynamics Group, University of Montpellier, 34293 Montpellier, France.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Centrosome, Cilia and Pathology Group, CRBM-CNRS, University of Montpellier, 34293 Montpellier, France anne.debant@crbm.cnrs.fr benedicte.delaval@crbm.cnrs.fr.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Delaval
authors.affiliation: Signaling and Cytoskeleton Dynamics Group, University of Montpellier, 34293 Montpellier, France anne.debant@crbm.cnrs.fr benedicte.delaval@crbm.cnrs.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Debant
mesh_terms: D000199:Actins / Q000378:metabolism; D048749:Cytokinesis; D020690:GTPase-Activating Proteins / Q000502:physiology*; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D059008:Time-Lapse Imaging
chemical_list: D000199:Actins; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; C115995:mgcRacGAP; D017346:Protein Serine-Threonine Kinases; C099628:TRIO protein, human