Compromised fidelity of endocytic synaptic vesicle protein sorting in the absence of stonin 2
Compromised fidelity of endocytic synaptic vesicle protein sorting in the absence of stonin 2
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DOI：
10.1073/pnas.1218432110
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发表时间：
2013-02-05
影响因子：
11.1
通讯作者：
Haucke, Volker
中科院分区：
文献类型：
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作者：
Kononenko, Natalia L.;Diril, M. Kasim;Haucke, Volker
神经传递依赖于突触囊泡（SV）的胞吐融合及其随后的重组，无论是通过网格蛋白介导的内吞作用还是从大量内体出芽。突触如何能够快速回收SV以保持SV池的大小，但保持其组成的身份，是知之甚少。我们证明，在小鼠中的内吞适配器stonin 2（Stn 2）的删除妥协的SV蛋白分选的保真度，而SV检索的表观速度增加。Stn2的丢失导致突触结合蛋白1选择性错配到神经元表面，SV池大小升高，SV蛋白内吞加速。后一种表型是通过过表达突触结合蛋白1的内吞缺陷变体来模仿的。在Stn2不存在的情况下SV蛋白回收的速度增加与SV从本体内体重组的上调相关。我们的研究结果是一致的模型，其中Stn2是需要保存SV蛋白质的组成，但维持SV回收的速度是不确定的。
Neurotransmission depends on the exocytic fusion of synaptic vesicles (SVs) and their subsequent reformation either by clathrin-mediated endocytosis or budding from bulk endosomes. How synapses are able to rapidly recycle SVs to maintain SV pool size, yet preserve their compositional identity, is poorly understood. We demonstrate that deletion of the endocytic adaptor stonin 2 (Stn2) in mice compromises the fidelity of SV protein sorting, whereas the apparent speed of SV retrieval is increased. Loss of Stn2 leads to selective missorting of synaptotagmin 1 to the neuronal surface, an elevated SV pool size, and accelerated SV protein endocytosis. The latter phenotype is mimicked by overexpression of endocytosis-defective variants of synaptotagmin 1. Increased speed of SV protein retrieval in the absence of Stn2 correlates with an up-regulation of SV reformation from bulk endosomes. Our results are consistent with a model whereby Stn2 is required to preserve SV protein composition but is dispensable for maintaining the speed of SV recycling.