Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons

Annika Lundström, Marco Gallio, Camilla Englund, Pär Steneberg, Johanna Hemphälä, Pontus Aspenström, Krystyna Keleman, Ludmilla Falileeva, Barry J. Dickson, Christos Samakovlis*

*Corresponding author for this work

Research output: Contribution to journalArticle

86 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2161-2171
Number of pages11
JournalGenes and Development
Volume18
Issue number17
DOIs
StatePublished - Sep 1 2004

Keywords

  • Cell migration
  • Drosophila
  • GTPase-activating protein
  • Rac
  • Robo
  • Slit

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Lundström, A., Gallio, M., Englund, C., Steneberg, P., Hemphälä, J., Aspenström, P., Keleman, K., Falileeva, L., Dickson, B. J., & Samakovlis, C. (2004). Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons. Genes and Development, 18(17), 2161-2171. https://doi.org/10.1101/gad.310204