Small GTPase Rab17 Regulates Dendritic Morphogenesis and Postsynaptic Development of Hippocampal Neurons
Small GTPase Rab17 Regulates Dendritic Morphogenesis and Postsynaptic Development of Hippocampal Neurons
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DOI：
10.1074/jbc.m111.314385
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发表时间：
2012-03-16
影响因子：
4.8
通讯作者：
Fukuda, Mitsunori
中科院分区：
文献类型：
--
作者：
Mori, Yasunori;Matsui, Takahide;Fukuda, Mitsunori
神经元在形态上、分子上和功能上被划分为两个不同的区域：轴突和树突，在这些区域内精确定位和定位蛋白质对于神经元的正常功能至关重要。据报道，RAB家族中的几个成员是膜转运的关键中介，它们调控轴突特异性转运事件，但关于树突特异性膜转运的分子机制尚不清楚。在这里，我们展示了Rab17调节小鼠海马神经元的树突形态发生和突触后发育。Rab17定位于树突状生长锥体、轴突、丝状柄和成熟棘细胞，但在轴突中大多缺失。我们还发现Rab17介导了树突的生长和分支，而不调节轴突的生长和分支。此外，shRNA介导的Rab17表达下调导致树突棘数量显著减少，这可能是因为丝状足的形成受到损害。这些发现揭示了膜运输和树突发生之间的第一个分子联系。
Neurons are compartmentalized into two morphologically, molecularly, and functionally distinct domains: axons and dendrites, and precise targeting and localization of proteins within these domains are critical for proper neuronal functions. It has been reported that several members of the Rab family small GTPases that are key mediators of membrane trafficking, regulate axon-specific trafficking events, but little has been elucidated regarding the molecular mechanisms that underlie dendrite-specific membrane trafficking. Here we show that Rab17 regulates dendritic morphogenesis and postsynaptic development in mouse hippocampal neurons. Rab17 is localized at dendritic growth cones, shafts, filopodia, and mature spines, but it is mostly absent in axons. We also found that Rab17 mediates dendrite growth and branching and that it does not regulate axon growth or branching. Moreover, shRNA-mediated knockdown of Rab17 expression resulted in a dramatically reduced number of dendritic spines, probably because of impaired filopodia formation. These findings have revealed the first molecular link between membrane trafficking and dendritogenesis.