BDNF regulates Rab11-mediated recycling endosome dynamics to induce dendritic branching.
BDNF regulates Rab11-mediated recycling endosome dynamics to induce dendritic branching.
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DOI：
10.1523/jneurosci.4630-12.2013
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发表时间：
2013-04-03
期刊：
影响因子：
--
通讯作者：
Bronfman FC
中科院分区：
文献类型：
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作者：
Lazo OM;Gonzalez A;Ascaño M;Kuruvilla R;Couve A;Bronfman FC
神经元的树突状分支由脑源性神经营养因子（BDNF）及其受体TrkB调节。内吞作用是树突状细胞分支所必需的，并调节TrkB信号，但内吞后运输如何决定神经元对BDNF的反应还不清楚。单体GTTRab 11调节再循环内体的动力学和受体向特定树突隔室的局部递送。我们的目的是研究是否Rab 11依赖运输的TrkB在树突调节BDNF诱导的大鼠海马神经元树突分支。我们报告说，TrkB在树突是Rab 11内体和Rab 11和其效应MyoVb的货物所需的BDNF/TrkB诱导的树突状分支。反过来，BDNF诱导Rab 11阳性内体和GTP结合的Rab 11在树突中积累。此外，Rab 11的组成型活性突变体的表达足以通过增加TrkB在树突中的定位和增强对内源性BDNF的敏感性来增加树突分支。我们认为Rab 11依赖的树突循环提供了一种机制，保留TrkB在树突和增加局部信号调节树枝化。
Dendritic arborization of neurons is regulated by brain-derived neurotrophic factor (BDNF) together with its receptor TrkB. Endocytosis is required for dendritic branching and regulates TrkB signaling, but how post-endocytic trafficking determine the neuronal response to BDNF is not well understood. The monomeric GTPase Rab11 regulates the dynamics of recycling endosomes and local delivery of receptors to specific dendritic compartments. Our aim was to study whether Rab11-dependent trafficking of TrkB in dendrites regulates BDNF-induced dendritic branching in rat hippocampal neurons. We report that TrkB in dendrites is a cargo for Rab11 endosomes and both Rab11 and its effector MyoVb are required for BDNF/TrkB-induced dendritic branching. In turn, BDNF induces accumulation of Rab11-positive endosomes and GTP-bound Rab11 in dendrites. Moreover, the expression of a constitutively active mutant of Rab11 is sufficient to increase dendritic branching by increasing TrkB localization in dendrites and enhancing sensitization to endogenous BDNF. We propose that Rab11-dependent dendritic recycling provides a mechanism to retain TrkB in dendrites and increase local signaling to regulate arborization.