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 | |
| State | Published - Oct 19 2001 |
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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 journal › Article
}
TY - JOUR
T1 - Signal transduction in neuronal migration
T2 - Roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway
AU - Wong, Kit
AU - Ren, Xiu Rong
AU - Huang, Yang Zhong
AU - Xie, Yi
AU - Liu, Guofa
AU - Saito, Harumi
AU - Tang, Hao
AU - Wen, Leng
AU - Brady-Kalnay, Susann M.
AU - Mei, Lin
AU - Wu, Jane Y.
AU - Xiong, Wencheng
AU - Rao, Yi
PY - 2001/10/19
Y1 - 2001/10/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=17944380009&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17944380009&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(01)00530-X
DO - 10.1016/S0092-8674(01)00530-X
M3 - Article
C2 - 11672528
AN - SCOPUS:17944380009
VL - 107
SP - 209
EP - 221
JO - Cell
JF - Cell
SN - 0092-8674
IS - 2
ER -