Author/Authors :
Kit Wong، نويسنده , , Xiu-Rong Ren، نويسنده , , Yang-Zhong Huang، نويسنده , , Yi Xie، نويسنده , , Guofa Liu، نويسنده , , Harumi Saito، نويسنده , , Hao Tang، نويسنده , , Leng Wen، نويسنده , , Susann M. Brady-Kalnay، نويسنده , , Lin Mei Tan، نويسنده , , Jane Y. Wu، نويسنده , , Wen-Cheng Xiong، نويسنده , , Yi Rao، نويسنده ,
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.
