Wragg Rachel T, Gouzer Géraldine, Bai Jihong, Arianna Gianluca, Ryan Timothy A, Dittman Jeremy S
Department of Biochemistry, Weill Cornell Medical College, New York, New York.
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Biophys J. 2015 Mar 24;108(6):1318-1329. doi: 10.1016/j.bpj.2014.12.057.
Nervous system function relies on precise chemical communication between neurons at specialized junctions known as synapses. Complexin (CPX) is one of a small number of cytoplasmic proteins that are indispensable in controlling neurotransmitter release through SNARE and synaptic vesicle interactions. However, the mechanisms that recruit and stabilize CPX are poorly understood. The mobility of CPX tagged with photoactivatable green fluorescent protein (pGFP) was quantified in vivo using Caenorhabditis elegans. Although pGFP escaped the synapse within seconds, CPX-pGFP displayed both fast and slow decay components, requiring minutes for complete exchange of the synaptic pool. The longer synaptic residence time of CPX arose from both synaptic vesicle and SNARE interactions, and surprisingly, CPX mobility depended on synaptic activity. Moreover, mouse CPX-GFP reversibly dispersed out of hippocampal presynaptic terminals during stimulation, and blockade of vesicle fusion prevented CPX dispersion. Hence, synaptic CPX can rapidly redistribute and this exchange is influenced by neuronal activity, potentially contributing to use-dependent plasticity.
神经系统的功能依赖于神经元在称为突触的特殊连接处进行精确的化学通讯。复合体蛋白（CPX）是少数几种通过SNARE与突触小泡相互作用来控制神经递质释放所必需的胞质蛋白之一。然而，招募和稳定CPX的机制却知之甚少。利用秀丽隐杆线虫在体内对用可光激活绿色荧光蛋白（pGFP）标记的CPX的流动性进行了定量分析。尽管pGFP在数秒内就从突触中逸出，但CPX-pGFP显示出快速和缓慢的衰减成分，突触池完全交换需要数分钟。CPX较长的突触停留时间源于突触小泡和SNARE的相互作用，令人惊讶的是，CPX的流动性取决于突触活动。此外，在刺激过程中，小鼠CPX-GFP可逆地从海马突触前终末分散开来，并且囊泡融合的阻断阻止了CPX的分散。因此，突触CPX可以快速重新分布，这种交换受神经元活动的影响，可能有助于依赖使用的可塑性。
