Molecular Dissection of the Semaphorin 4D Receptor Plexin-B1-Stimulated R-Ras GTPase-Activating Protein Activity and Neurite Remodeling in Hippocampal Neurons
Open Access
- 15 December 2004
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 24 (50), 11473-11480
- https://doi.org/10.1523/jneurosci.3257-04.2004
Abstract
Plexins serve as receptors for repulsive axonal guidance molecules semaphorins. The cytoplasmic domain of the semaphorin 4D (Sema4D) receptor, Plexin-B1 has two separated Ras GTPase-activating protein (GAP)-homologous domains, C1 and C2. Recently, we reported that the Rho family small GTPase Rnd1 associates with Plexin-B1, and the Plexin-B1-Rnd1 complex stimulates GTPase activity of R-Ras, inducing growth cone collapse in hippocampal neurons in response to Sema4D. However, the molecular mechanisms by which Plexin-B1 exhibits the GAP activity remain unclear. In this report, critical roles of Rnd1 and Sema4D in Plexin-B1-stimulated R-Ras GAP activity and neurite remodeling were examined. The N-terminal region of the cytoplasmic domain of Plexin-B1 containing the C1 domain interacts with the C-terminal region containing the C2 domain, and Rnd1 disrupts this interaction. On the other hand, Sema4D induces clustering of Rnd1-bound Plexin-B1, in parallel with inactivation of R-Ras in cells. Antibody clustering of the recombinant cytoplasmic domain of Plexin-B1 in the presence of Rnd1 triggers the R-Ras GAP activity. Deletion of the extracellular domain of Plexin-B1 causes ligand-independent clustering of the receptor, rendering the receptor constitutively active in the presence of Rnd1, and induces contraction of COS-7 cells and inhibition of neurite outgrowth in hippocampal neurons. These results indicate that Rnd1 opens the two R-Ras GAP domains of Plexin-B1, and Sema4D-induced receptor clustering stimulates R-Ras GAP activity and neurite remodeling in hippocampal neurons.Keywords
This publication has 36 references indexed in Scilit:
- The Semaphorin 4D Receptor Plexin-B1 Is a GTPase Activating Protein for R-RasScience, 2004
- Plexin signaling hampers integrin‐based adhesion, leading to Rho‐kinase independent cell rounding, and inhibiting lamellipodia extension and cell motilityThe FASEB Journal, 2004
- Ras GTPases: integrins' friends or foes?Nature Reviews Molecular Cell Biology, 2003
- Direct Interaction of Rnd1 with Plexin-B1 Regulates PDZ-RhoGEF-mediated Rho Activation by Plexin-B1 and Induces Cell Contraction in COS-7 CellsJournal of Biological Chemistry, 2003
- Rho GTPases in cell biologyNature, 2002
- Plexin B Regulates Rho through the Guanine Nucleotide Exchange Factors Leukemia-associated Rho GEF (LARG) and PDZ-RhoGEFJournal of Biological Chemistry, 2002
- Socius Is a Novel Rnd GTPase-Interacting Protein Involved in Disassembly of Actin Stress FibersMolecular and Cellular Biology, 2002
- The semaphorin receptor plexin-B1 specifically interacts with active Rac in a ligand-dependent mannerProceedings of the National Academy of Sciences, 2000
- Regulatory Proteins of R-Ras, TC21/R-Ras2, and M-Ras/R-Ras3Journal of Biological Chemistry, 2000
- Integrin Activation by R-rasCell, 1996