title: Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons.
abstract: Slit proteins steer the migration of many cell types through their binding to Robo receptors, but how Robo controls cell motility is not clear. We describe the functional analysis of vilse, a Drosophila gene required for Robo repulsion in epithelial cells and axons. Vilse defines a conserved family of RhoGAPs (Rho GTPase-activating proteins), with representatives in flies and vertebrates. The phenotypes of vilse mutants resemble the tracheal and axonal phenotypes of Slit and Robo mutants at the CNS midline. Dosage-sensitive genetic interactions between vilse, slit, and robo mutants suggest that vilse is a component of robo signaling. Moreover, overexpression of Vilse in the trachea of robo mutants ameliorates the phenotypes of robo, indicating that Vilse acts downstream of Robo to mediate midline repulsion. Vilse and its human homolog bind directly to the intracellular domains of the corresponding Robo receptors and promote the hydrolysis of RacGTP and, less efficiently, of Cdc42GTP. These results together with genetic interaction experiments with robo, vilse, and rac mutants suggest a mechanism whereby Robo repulsion is mediated by the localized inactivation of Rac through Vilse.
authors.affiliation: Department of Developmental Biology, Wenner-Gren Institute, Stockholm University, S-106 96 Stockholm, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Lundström
authors.forename: Marco
authors.initials: M
authors.lastname: Gallio
authors.forename: Camilla
authors.initials: C
authors.lastname: Englund
authors.forename: Pär
authors.initials: P
authors.lastname: Steneberg
authors.forename: Johanna
authors.initials: J
authors.lastname: Hemphälä
authors.forename: Pontus
authors.initials: P
authors.lastname: Aspenström
authors.forename: Krystyna
authors.initials: K
authors.lastname: Keleman
authors.forename: Ludmilla
authors.initials: L
authors.lastname: Falileeva
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Dickson
authors.forename: Christos
authors.initials: C
authors.lastname: Samakovlis
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D015139:Blotting, Southern; D002465:Cell Movement / Q000502:physiology*; D002490:Central Nervous System / Q000502:physiology; D017931:DNA Primers; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005982:Glutathione Transferase; D017403:In Situ Hybridization; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000502:physiology; D011971:Receptors, Immunologic / Q000378:metabolism* / Q000502:physiology; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology; D020798:Two-Hybrid System Techniques; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; D005982:Glutathione Transferase; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D000097905:Roundabout Proteins; C066819:sli protein, Drosophila