Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology

Neuron. 2002 Jul 3;35(1):51-63. doi: 10.1016/s0896-6273(02)00750-x.

Abstract

Plexins are widely expressed transmembrane proteins that, in the nervous system, mediate repulsive signals of semaphorins. However, the molecular nature of plexin-mediated signal transduction remains poorly understood. Here, we demonstrate that plexin-B family members associate through their C termini with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. Activation of plexin-B1 by semaphorin 4D regulates PDZ-RhoGEF/LARG activity leading to RhoA activation. In addition, a dominant-negative form of PDZ-RhoGEF blocks semaphorin 4D-induced growth cone collapse in primary hippocampal neurons. Our study indicates that the interaction of mammalian plexin-B family members with the multidomain proteins PDZ-RhoGEF and LARG represents an essential molecular link between plexin-B and localized, Rho-mediated downstream signaling events which underly various plexin-mediated cellular phenomena including axonal growth cone collapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD*
  • Cell Communication / genetics*
  • Cell Differentiation / genetics*
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Chick Embryo
  • Fetus
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Hippocampus / embryology*
  • Hippocampus / growth & development
  • Hippocampus / metabolism
  • Humans
  • Immunohistochemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding / genetics
  • Protein Structure, Tertiary / genetics
  • Rats
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Retinal Ganglion Cells / cytology
  • Retinal Ganglion Cells / metabolism
  • Rho Guanine Nucleotide Exchange Factors
  • Semaphorins*
  • Signal Transduction / genetics*
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • ARHGEF12 protein, human
  • Antigens, CD
  • CD100 antigen
  • Guanine Nucleotide Exchange Factors
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • PLXNB1 protein, human
  • RAPGEF2 protein, human
  • Receptors, Cell Surface
  • Rho Guanine Nucleotide Exchange Factors
  • Semaphorins
  • rhoA GTP-Binding Protein