title: Gem GTPase acts upstream Gmip/RhoA to regulate cortical actin remodeling and spindle positioning during early mitosis.
abstract: Gem is a small guanosine triphosphate (GTP)-binding protein within the Ras superfamily, involved in the regulation of voltage-gated calcium channel activity and cytoskeleton reorganization. Gem overexpression leads to stress fiber disruption, actin and cell shape remodeling and neurite elongation in interphase cells. In this study, we show that Gem plays a crucial role in the regulation of cortical actin cytoskeleton that undergoes active remodeling during mitosis. Ectopic expression of Gem leads to cortical actin disruption and spindle mispositioning during metaphase. The regulation of spindle positioning by Gem involves its downstream effector Gmip. Knockdown of Gmip rescued Gem-induced spindle phenotype, although both Gem and Gmip accumulated at the cell cortex. In addition, we implicated RhoA GTPase as an important effector of Gem/Gmip signaling. Inactivation of RhoA by overexpressing dominant-negative mutant prevented normal spindle positioning. Introduction of active RhoA rescued the actin and spindle positioning defects caused by Gem or Gmip overexpression. These findings demonstrate a new role of Gem/Gmip/RhoA signaling in cortical actin regulation during early mitotic stages.
authors.affiliation: Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), CNRS, F-31062 Toulouse, France, CNRS, Institut de Pharmacologie et de Biologie Structurale (IPBS), UMR 5089, 205 route de Narbonne, BP 64182, F-31077 Toulouse, France and Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Andrieu
authors.affiliation: Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), CNRS, F-31062 Toulouse, France, Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Quaranta
authors.affiliation: Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), CNRS, F-31062 Toulouse, France, Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Leprince
authors.affiliation: CNRS, Institut de Pharmacologie et de Biologie Structurale (IPBS), UMR 5089, 205 route de Narbonne, BP 64182, F-31077 Toulouse, France and Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cuvillier
authors.affiliation: Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), CNRS, F-31062 Toulouse, France, CNRS, Institut de Pharmacologie et de Biologie Structurale (IPBS), UMR 5089, 205 route de Narbonne, BP 64182, F-31077 Toulouse, France and Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France anastassia.hatzoglou@ipbs.fr.
authors.forename: Anastassia
authors.initials: A
authors.lastname: Hatzoglou
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000096:biosynthesis* / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D008941:Spindle Apparatus / Q000235:genetics; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C474310:GMIP protein, human; D020690:GTPase-Activating Proteins; D024642:Potassium Channels, Voltage-Gated; C066737:RHOA protein, human; D020558:GTP Phosphohydrolases; D020742:rhoA GTP-Binding Protein