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

doi:10.1016/S0092-8674(01)00530-X

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

Graduate Studies

Research output: Contribution to journal › Article

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 language	English (US)
Pages (from-to)	209-221
Number of pages	13
Journal	Cell
Volume	107
Issue number	2
DOIs	https://doi.org/10.1016/S0092-8674(01)00530-X
State	Published - 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

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 journal › Article

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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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.",

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

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