通过Rho-GEF kalirin的反式突触 EphrinB-EphB受体激活快速诱导树突棘形态发生

Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin.

作者信息

Penzes Peter, Beeser Alexander, Chernoff Jonathan, Schiller Martin R, Eipper Betty A, Mains Richard E, Huganir Richard L

机构信息

Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.

出版信息

Neuron. 2003 Jan 23;37(2):263-74. doi: 10.1016/s0896-6273(02)01168-6.

DOI:10.1016/s0896-6273(02)01168-6

PMID:12546821

Abstract

The morphogenesis of dendritic spines, the major sites of excitatory synaptic transmission in the brain, is important in synaptic development and plasticity. We have identified an ephrinB-EphB receptor trans-synaptic signaling pathway which regulates the morphogenesis and maturation of dendritic spines in hippocampal neurons. Activation of the EphB receptor induces translocation of the Rho-GEF kalirin to synapses and activation of Rac1 and its effector PAK. Overexpression of dominant-negative EphB receptor, catalytically inactive kalirin, or dominant-negative Rac1, or inhibition of PAK eliminates ephrin-induced spine development. This novel signal transduction pathway may be critical for the regulation of the actin cytoskeleton controlling spine morphogenesis during development and plasticity.

摘要

树突棘是大脑中兴奋性突触传递的主要部位，其形态发生在突触发育和可塑性方面具有重要意义。我们已经确定了一种 EphrinB-EphB 受体跨突触信号通路，该通路调节海马神经元中树突棘的形态发生和成熟。EphB 受体的激活会诱导 Rho-GEF 卡利林向突触转位，并激活 Rac1 及其效应器 PAK。显性负性 EphB 受体、催化失活的卡利林或显性负性 Rac1 的过表达，或 PAK 的抑制，都会消除 Ephrin 诱导的棘突发育。这种新的信号转导通路可能对发育和可塑性过程中控制棘突形态发生的肌动蛋白细胞骨架的调节至关重要。