The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras.
Plexins are cell surface receptors for semaphorin molecules, and their interaction governs cell adhesion and migration in a variety of tissues. We report that the Semaphorin 4D (Sema4D) receptor Plexin-B1 directly stimulates the intrinsic guanosine triphosphatase (GTPase) activity of R-Ras, a member of the Ras superfamily of small GTP-binding proteins that has been implicated in promoting cell adhesion and neurite outgrowth. This activity required the interaction of Plexin-B1 with Rnd1, a small GTP-binding protein of the Rho family. Down-regulation of R-Ras activity by the Plexin-B1-Rnd1 complex was essential for the Sema4D-induced growth cone collapse in hippocampal neurons. Thus, Plexin-B1 mediates Sema4D-induced repulsive axon guidance signaling by acting as a GTPase activating protein for R-Ras.
Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Izumi
I
Oinuma
Yukio
Y
Ishikawa
Hironori
H
Katoh
Manabu
M
Negishi
D000818:Animals; D015703:Antigens, CD; D001369:Axons / Q000502:physiology; D019556:COS Cells; D002478:Cells, Cultured; D015536:Down-Regulation; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D039961:Semaphorins; D015398:Signal Transduction; D014162:Transfection; D018631:ras Proteins / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D015703:Antigens, CD; C093224:CD100 antigen; D020690:GTPase-Activating Proteins; D008562:Membrane Glycoproteins; C488752:Plxnb1 protein, rat; D034741:RNA, Small Interfering; C491772:RND1 protein, human; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C491771:Rnd1 protein, rat; D039961:Semaphorins; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; C085929:RRAS protein, human; D018631:ras Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein