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Plexins are cell surface receptors for semaphorin molecules,and their interaction governs cell adhesion and migration ina variety of tissues. We report that the Semaphorin 4D (Sema4D)receptor Plexin-B1 directly stimulates the intrinsic guanosinetriphosphatase (GTPase) activity of R-Ras, a member of the Rassuperfamily of small GTP-binding proteins that has been implicatedin promoting cell adhesion and neurite outgrowth. This activityrequired the interaction of Plexin-B1 with Rnd1, a small GTP-bindingprotein of the Rho family. Down-regulation of R-Ras activityby the Plexin-B1-Rnd1 complex was essential for the Sema4D-inducedgrowth cone collapse in hippocampal neurons. Thus, Plexin-B1mediates Sema4D-induced repulsive axon guidance signaling byacting as a GTPase activating protein for R-Ras.
Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
* To whom correspondence should be addressed. E-mail address: mnegishi{at}pharm.kyoto-u.ac.jp
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