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


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wong, K; Ren, XR; Huang, YZ; Xie, Y; Liu, G; Saito, H; Tang, H; Wen, L; Brady-Kalnay, SM; Mei, L; Wu, JY; Xiong, WC; Rao, Y

Published Date

  • October 19, 2001

Published In

Volume / Issue

  • 107 / 2

Start / End Page

  • 209 - 221

PubMed ID

  • 11672528

Pubmed Central ID

  • 11672528

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/s0092-8674(01)00530-x


  • eng

Conference Location

  • United States