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RhoA 信号通路调控树突高尔基体末梢形成。

A RhoA Signaling Pathway Regulates Dendritic Golgi Outpost Formation.

机构信息

Laboratorio Neurobiología, INIMEC-CONICET, Av. Friuli 2434, 5016 Córdoba, Argentina; Universidad Nacional de Córdoba, Av. Haya de la Torre s/n, 5000 Córdoba, Argentina.

Programa de Fisiología y Biofísica, Instituto de Ciencias Biomédicas, Biomedical Neuroscience Institute, Facultad de Medicina, Universidad de Chile, Independencia 1027, 8380453 Santiago, Chile.

出版信息

Curr Biol. 2015 Apr 20;25(8):971-82. doi: 10.1016/j.cub.2015.01.075. Epub 2015 Mar 19.

Abstract

The neuronal Golgi apparatus (GA) localizes to the perinuclear region and dendrites as tubulo-vesicular structures designated Golgi outposts (GOPs). Current evidence suggests that GOPs shape dendrite morphology and serve as platforms for the local delivery of synaptic receptors. However, the mechanisms underlying GOP formation remain a mystery. Using live-cell imaging and confocal microscopy in cultured hippocampal neurons, we now show that GOPs destined to major "apical" dendrites are generated from the somatic GA by a sequence of events involving: (1) generation of a GA-derived tubule; (2) tubule elongation and deployment into the dendrite; (3) tubule fission; and (4) transport and condensation of the fissioned tubule. A RhoA-Rock signaling pathway involving LIMK1, PKD1, slingshot, cofilin, and dynamin regulates polarized GOP formation by controlling the tubule fission. Our observations identify a mechanism underlying polarized GOP biogenesis and provide new insights regarding involvement of RhoA in dendritic development and polarization.

摘要

神经元高尔基器(GA)定位于核周区域和树突,作为管状-泡状结构,被称为高尔基末梢(GOPs)。目前的证据表明,GOPs 塑造树突形态,并作为局部递送突触受体的平台。然而,GOP 形成的机制仍然是一个谜。我们现在通过在培养的海马神经元中使用活细胞成像和共聚焦显微镜显示, destined to major "apical" dendrites 的 GOPs 是通过一系列事件从体细胞 GA 产生的,这些事件包括:(1)产生一个源自 GA 的小管;(2)小管伸长并部署到树突中;(3)小管分裂;(4)分裂小管的运输和浓缩。RhoA-Rock 信号通路涉及 LIMK1、PKD1、slingshot、cofilin 和 dynamin,通过控制小管分裂来调节极化 GOP 的形成。我们的观察结果确定了极化 GOP 生物发生的机制,并提供了关于 RhoA 参与树突发育和极化的新见解。

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