The Semaphorin 4D Receptor Plexin-B1 Is a GTPase Activating Protein for R-Ras

• Published in: Science (American Association for the Advancement of Science) 2004-08, Vol.305 (5685), p.862-865
• Main Authors: Oinuma, Izumi, Ishikawa, Yukio, Katoh, Hironori, Negishi, Manabu
• Format: Article
• Language: English
• Subjects: Anatomy; Animals; Antibodies; Antigens, CD; Axons - physiology; Biological and medical sciences; Cell adhesion & migration; Cell interaction; Cell interactions; Cell interactions, adhesion; Cells, Cultured; COS Cells; Down regulation; Fundamental and applied biological sciences. Psychology; Growth cones; GTP Phosphohydrolases - metabolism; GTPase-Activating Proteins - chemistry; GTPase-Activating Proteins - genetics; GTPase-Activating Proteins - metabolism; Guanosine Triphosphate - metabolism; Hippocampus - cytology; Humans; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - pharmacology; Membrane proteins; Migration; Molecular and cellular biology; Molecules; Mutation; Neurites; Neurites - physiology; Neurons; Neurons - metabolism; PC12 Cells; Plasmids; Properties; Protein Structure, Tertiary; Proteins; ras Proteins - metabolism; Rats; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Recombinant Fusion Proteins - metabolism; Resident Advisers; rho GTP-Binding Proteins - genetics; rho GTP-Binding Proteins - metabolism; rhoA GTP-Binding Protein - metabolism; RNA, Small Interfering; Semaphorins; Signal Transduction; Small interfering RNA; Transfection
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1097545

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.