Rab33a Mediates Anterograde Vesicular Transport for Membrane Exocytosis and Axon Outgrowth
Rab33a Mediates Anterograde Vesicular Transport for Membrane Exocytosis and Axon Outgrowth
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DOI：
10.1523/jneurosci.0989-12.2012
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发表时间：
2012-09-12
影响因子：
5.3
通讯作者：
Inagaki, Naoyuki
中科院分区：
文献类型：
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作者：
Nakazawa, Hitomi;Sada, Tadayuki;Inagaki, Naoyuki
轴突生长需要质膜扩张，这是高尔基体后囊泡运输和融合的结果。然而，调节后高尔基体囊泡运输膜扩张和轴突生长的分子机制仍不清楚。在这里，我们发现Rab33a的表达在培养的大鼠海马神经元轴突生长过程中上调。Rab33 a优先定位于高尔基体和突触体蛋白阳性囊泡，这些囊泡沿着生长的轴突运输。以往的研究表明，突触体蛋白定位于高尔基体后囊泡的快速轴突运输在发育中的神经元。通过RNAi（RNA干扰）减少Rab33a的表达抑制了突触体蛋白阳性囊泡的顺行运输，导致其在轴突尖端的减少。此外，这种治疗减少了生长锥中突触素阳性囊泡的膜融合，并抑制了轴突生长。Rab33a的过度表达，另一方面，诱导过度积累的突触体蛋白阳性囊泡和同时形成过剩的轴突。这些数据表明，Rab33a通过介导突触泡蛋白阳性囊泡的顺行轴突运输及其伴随的生长锥融合参与轴突生长。
Axon outgrowth requires plasma membrane expansion, which results from post-Golgi vesicular transport and fusion. However, the molecular mechanisms regulating post-Golgi vesicular trafficking for membrane expansion and axon outgrowth remain unclear. Here, we show that Rab33a expression became upregulated during axon outgrowth of cultured rat hippocampal neurons. Rab33a was preferentially localized to the Golgi apparatus and to synaptophysin-positive vesicles that are transported along the growing axon. Previous studies showed that synaptophysin is localized to post-Golgi vesicles transported by fast axonal transport in developing neurons. Reduction of Rab33a expression by RNAi (RNA interference) inhibited the anterograde transport of synaptophysin-positive vesicles, leading to their decrease in axonal tips. Furthermore, this treatment reduced membrane fusion of synaptophysin-positive vesicles at the growth cones and inhibited axon outgrowth. Overexpression of Rab33a, on the other hand, induced excessive accumulation of synaptophysin-positive vesicles and concurrent formation of surplus axons. These data suggest that Rab33a participates in axon outgrowth by mediating anterograde axonal transport of synaptophysin-positive vesicles and their concomitant fusion at the growth cones.