Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
J Biol Chem. 2012 Mar 16;287(12):8963-73. doi: 10.1074/jbc.M111.314385. Epub 2012 Jan 30.
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.
神经元分为两个形态、分子和功能上不同的区域：轴突和树突，而这些区域内的蛋白质的精确靶向和定位对于神经元的正常功能至关重要。已经报道了 Rab 家族的几个小 GTPase 成员，它们是膜运输的关键介质，调节轴突特异性的运输事件，但关于支持树突特异性膜运输的分子机制还知之甚少。在这里，我们显示 Rab17 调节小鼠海马神经元的树突形态发生和突触后发育。Rab17 定位于树突生长锥、轴突、丝状伪足和成熟的棘突，但在轴突中几乎不存在。我们还发现 Rab17 介导树突生长和分支，而不调节轴突生长或分支。此外，shRNA 介导的 Rab17 表达敲低导致树突棘的数量显著减少，可能是由于丝状伪足形成受损所致。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。
