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

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.
Mesh Terms:
Animals, Antigens, CD, Cell Communication, Cell Differentiation, Cell Membrane, Cells, Cultured, Chick Embryo, Fetus, Growth Cones, Guanine Nucleotide Exchange Factors, Hippocampus, Humans, Immunohistochemistry, Membrane Glycoproteins, Mutation, Nerve Tissue Proteins, Protein Binding, Protein Structure, Tertiary, Rats, Receptors, Cell Surface, Retinal Ganglion Cells, Semaphorins, Signal Transduction, rhoA GTP-Binding Protein
Neuron
Date: Jul. 03, 2002
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