Motorneurons Require Cysteine String Protein-α to Maintain the Readily Releasable Vesicular Pool and Synaptic Vesicle Recycling
Motorneurons Require Cysteine String Protein-α to Maintain the Readily Releasable Vesicular Pool and Synaptic Vesicle Recycling
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DOI：
10.1016/j.neuron.2012.02.019
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发表时间：
2012-04-12
期刊：
影响因子：
16.2
通讯作者：
Fernandez-Chacon, Rafael
中科院分区：
文献类型：
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作者：
Luis Rozas, Jose;Gomez-Sanchez, Leonardo;Fernandez-Chacon, Rafael
半胱氨酸串蛋白-α（CSP-alpha）是一种突触囊泡蛋白，其通过知之甚少的机制防止活动依赖性神经变性。我们研究了表达synaptopHluorin转基因的CSP-α基因敲除小鼠的运动神经末梢的突触囊泡周期。突变的神经末梢不能维持长时间的释放，并且可被释放的囊泡的数量减少。引人注目的是，SNARE蛋白SNAP-25显著减少。此外，在刺激期间的内吞作用未能维持回收突触囊泡池的大小在延长的刺激。在去极化时，苯乙烯基染料FM 2-10被捕获并且难以释放。与功能结果一致，电子显微镜分析显示受损的突触囊泡回收的特征。CSP-α基因敲除小鼠中囊泡再循环的意外缺陷为理解运动神经末梢变性的分子机制提供了见解。
Cysteine string protein-alpha (CSP-alpha) is a synaptic vesicle protein that prevents activity-dependent neurodegeneration by poorly understood mechanisms. We have studied the synaptic vesicle cycle at the motor nerve terminals of CSP-alpha knock-out mice expressing the synaptopHluorin transgene. Mutant nerve terminals fail to sustain prolonged release and the number of vesicles available to be released decreases. Strikingly, the SNARE protein SNAP-25 is dramatically reduced. In addition, endocytosis during the stimulus fails to maintain the size of the recycling synaptic vesicle pool during prolonged stimulation. Upon depolarization, the styryl dye FM 2-10 becomes trapped and poorly releasable. Consistently with the functional results, electron microscopy analysis revealed characteristic features of impaired synaptic vesicle recycling. The unexpected defect in vesicle recycling in CSP-alpha knockout mice provides insights into understanding molecular mechanisms of degeneration in motor nerve terminals.