Vilse, a Conserved Rac/Cdc42 GAP Mediating Robo Repulsion in Tracheal Cells and Axons

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2004 Sep 3

PMID 15342493

Citations 63

Authors

Annika Lundstrom

Marco Gallio

Camilla Englund

Par Steneberg

Johanna Hemphala

Pontus Aspenstrom

Krystyna Keleman

Ludmilla Falileeva

Barry J Dickson

Christos Samakovlis

Affiliations

Soon will be listed here.

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.

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