Snapin recruits dynein to BDNF-TrkB signaling endosomes for retrograde axonal transport and is essential for dendrite growth of cortical neurons.
Snapin recruits dynein to BDNF-TrkB signaling endosomes for retrograde axonal transport and is essential for dendrite growth of cortical neurons.
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DOI：
10.1016/j.celrep.2012.06.010
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发表时间：
2012-07-26
期刊：
影响因子：
8.8
通讯作者：
Sheng ZH
中科院分区：
文献类型：
--
作者：
Zhou B;Cai Q;Xie Y;Sheng ZH
神经营养因子信号对神经元的生长至关重要。虽然“信号内体”假说是公认的模型之一，但驱动TrkB信号内体逆行轴突运输的分子机制在很大程度上是未知的。特别是，将dynein招募到TrkB信号内体的机制尚未阐明。在这里，我们利用Snapin缺陷小鼠和基因拯救实验，结合活体皮质神经元的分区培养，揭示了Snapin作为动力蛋白适配器，介导了TrkB信号内小体的逆行轴突运输。这种作用对于皮质神经元的树突状生长是必不可少的。删除Snapin或破坏Snapin-dynein相互作用会取消TrkB的逆行运输，削弱BDNF诱导的轴突终末到细胞核的逆行信号，并减少树突生长。通过重新引入Snapin基因，这些缺陷被拯救了。我们的研究表明，Snapin-dynein偶联是驱动BDNF-TrkB逆行转运的主要机制之一，从而为调控神经元的生长和存活提供了新的机制。
Neurotrophin signaling is crucial for neuron growth. While “signaling endosomes” hypothesis is one of accepted models, the molecular machinery that drives retrograde axonal transport of TrkB signaling endosomes is largely unknown. In particular, mechanisms recruiting dynein to TrkB signaling endosomes have not been elucidated. Here, using snapin deficient mice and gene rescue experiments combined with compartmentalized cultures of live cortical neurons, we reveal that Snapin, as a dynein adaptor, mediates retrograde axonal transport of TrkB signaling endosomes. Such a role is essential for dendritic growth of cortical neurons. Deleting snapin or disrupting Snapin-dynein interaction abolishes TrkB retrograde transport, impairs BDNF-induced retrograde signaling from axonal terminals to the nucleus, and decreases dendritic growth. Such defects were rescued by reintroducing snapin gene. Our study indicates that Snapin-dynein coupling is one of the primary mechanisms driving BDNF-TrkB retrograde transport, thus providing new mechanistic insights into the regulation of neuronal growth and survival.
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