Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway.

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.
Mesh Terms:
Actins, Amino Acid Sequence, Blotting, Northern, Cell Line, Cell Membrane, Cell Movement, Drosophila Proteins, GTP Phosphohydrolases, Genes, Dominant, Humans, Models, Biological, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Neurons, Protein Binding, Protein Structure, Tertiary, RNA, Messenger, Receptors, Immunologic, Retroviridae, Sequence Homology, Amino Acid, Signal Transduction, Tissue Distribution, Two-Hybrid System Techniques, cdc42 GTP-Binding Protein
Cell
Date: Oct. 19, 2001
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