期刊
CELL
卷 107, 期 2, 页码 209-221出版社
CELL PRESS
DOI: 10.1016/S0092-8674(01)00530-X
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资金
- NCI NIH HHS [R01 CA114197-01A2] Funding Source: Medline
- NEI NIH HHS [R01 EY014576-03] Funding Source: Medline
- NIGMS NIH HHS [R01 GM070967-02] Funding Source: Medline
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.
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