[HTML][HTML] Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology
Neuron, 2002•cell.com
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 …
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 …
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.
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