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

Research output: Contribution to journalArticle

415 Citations (Scopus)

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

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GTPase-Activating Proteins
Signal transduction
Monomeric GTP-Binding Proteins
Signal Transduction
Lateral Ventricles
Prosencephalon
Polymerization
Cues
Actins
Leukocytes
Proteins
rho GTPase-activating protein

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Signal transduction in neuronal migration : Roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway. / Wong, Kit; Ren, Xiu Rong; Huang, Yang Zhong; Xie, Yi; Liu, Guofa; Saito, Harumi; Tang, Hao; Wen, Leng; Brady-Kalnay, Susann M.; Mei, Lin; Wu, Jane Y.; Xiong, Wencheng; Rao, Yi.

In: Cell, Vol. 107, No. 2, 19.10.2001, p. 209-221.

Research output: Contribution to journalArticle

Wong, K, Ren, XR, Huang, YZ, Xie, Y, Liu, G, Saito, H, Tang, H, Wen, L, Brady-Kalnay, SM, Mei, L, Wu, JY, 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, vol. 107, no. 2, pp. 209-221. https://doi.org/10.1016/S0092-8674(01)00530-X
Wong, Kit ; Ren, Xiu Rong ; Huang, Yang Zhong ; Xie, Yi ; Liu, Guofa ; Saito, Harumi ; Tang, Hao ; Wen, Leng ; Brady-Kalnay, Susann M. ; Mei, Lin ; Wu, Jane Y. ; Xiong, Wencheng ; Rao, Yi. / Signal transduction in neuronal migration : Roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway. In: Cell. 2001 ; Vol. 107, No. 2. pp. 209-221.
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