Abstract
The Slit protein guides neuronal and leukocyte migration through the transmembrane receptor Roundabout (Robo). We report here that the intracellular domain of Robo interacts with a novel family of Rho GTPase activating proteins (GAPs). Two of the Slit-Robo GAPs (srGAPs) are expressed in regions responsive to Slit. Slit increased srGAP1-Robo1 interaction and inactivated Cdc42. A dominant negative srGAP1 blocked Slit inactivation of Cdc42 and Slit repulsion of migratory cells from the anterior subventricular zone (SVZa) of the forebrain. A constitutively active Cdc42 blocked the repulsive effect of Slit. These results have demonstrated important roles for GAPs and Cdc42 in neuronal migration. We propose a signal transduction pathway from the extracellular guidance cue to intracellular actin polymerization.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / metabolism
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Amino Acid Sequence
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Blotting, Northern
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Cell Line
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Cell Membrane / metabolism
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Cell Movement*
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Drosophila Proteins*
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GTP Phosphohydrolases / metabolism*
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Genes, Dominant
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Humans
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Models, Biological
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Molecular Sequence Data
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Mutation
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Nerve Tissue Proteins / metabolism*
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Neurons / cytology*
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Protein Binding
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Protein Structure, Tertiary
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RNA, Messenger / metabolism
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Receptors, Immunologic / metabolism*
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Retroviridae / genetics
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Roundabout Proteins
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Sequence Homology, Amino Acid
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Signal Transduction*
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Tissue Distribution
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Two-Hybrid System Techniques
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cdc42 GTP-Binding Protein / metabolism*
Substances
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Actins
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Drosophila Proteins
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Nerve Tissue Proteins
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RNA, Messenger
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Receptors, Immunologic
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sli protein, Drosophila
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GTP Phosphohydrolases
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cdc42 GTP-Binding Protein
Associated data
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GENBANK/AY057898
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GENBANK/AY057899
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GENBANK/AY057900