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

Kit Wong, Xiu Rong Ren, Yang Zhong Huang, Yi Xie, Guofa Liu, Harumi Saito, Hao Tang, Leng Wen, Susann M. Brady-Kalnay, Lin Mei, Jane Y. Wu, Wencheng Xiong, Yi Rao

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423 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)209-221
Number of pages13
JournalCell
Volume107
Issue number2
DOIs
StatePublished - Oct 19 2001

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Wong, K., Ren, X. R., Huang, Y. Z., Xie, Y., Liu, G., Saito, H., Tang, H., Wen, L., Brady-Kalnay, S. M., Mei, L., Wu, J. Y., Xiong, W., & Rao, Y. (2001). Signal transduction in neuronal migration: Roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway. Cell, 107(2), 209-221. https://doi.org/10.1016/S0092-8674(01)00530-X