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

• 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.

Ämnesord

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

Nyckelord

Animals

Axons/*metabolism/physiology

Blotting; Southern

Cell Movement/*physiology

Central Nervous System/physiology

Comparative Study

DNA Primers

Drosophila

Drosophila Proteins/*metabolism/physiology

Epithelial Cells/physiology

GTPase-Activating Proteins/genetics/*metabolism/physiology

Glutathione Transferase

In Situ Hybridization

Mutation/genetics

Nerve Tissue Proteins/*metabolism/physiology

Receptors; Immunologic/*metabolism/physiology

Research Support; Non-U.S. Gov't

Sequence Analysis; DNA

Signal Transduction/physiology

Two-Hybrid System Techniques

cdc42 GTP-Binding Protein/metabolism

rac GTP-Binding Proteins/metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)