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Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons
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2004 (English)In: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 18, no 17, 2161-2171 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2004. Vol. 18, no 17, 2161-2171 p.
Keyword [en]
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
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-73067DOI: 10.1101/gad.310204PubMedID: 15342493OAI: oai:DiVA.org:uu-73067DiVA: diva2:100978
Available from: 2005-05-31 Created: 2005-05-31 Last updated: 2013-11-05Bibliographically approved

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Aspenström, Pontus

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