Synapsin selectively controls the mobility of resting pool vesicles at hippocampal terminals.
Synapsin selectively controls the mobility of resting pool vesicles at hippocampal terminals.
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DOI：
10.1523/jneurosci.5058-11.2012
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发表时间：
2012-03-21
期刊：
影响因子：
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通讯作者：
Gitler D
中科院分区：
文献类型：
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作者：
Orenbuch A;Shalev L;Marra V;Sinai I;Lavy Y;Kahn J;Burden JJ;Staras K;Gitler D
突触前终末是信息传递的专门场所，在这里囊泡与质膜融合并在局部循环。最近的研究扩展了这一经典观点，观察到功能性囊泡的子集通过侧轴突运输在相邻终末之间动态共享。从概念上讲，这种运输可能会破坏活性区周围的囊泡保留，但终端的特点是高密度的囊泡簇，这表明对抗稳定机制必须对这种趋势起作用。突触蛋白是一类与突触囊泡相关并决定末端囊泡数量的蛋白，但其具体功能仍有争议。在这里，使用多种基于荧光的定量方法和电子显微镜，我们表明突触蛋白有助于抵抗囊泡分散，并作为控制突触之间侧囊泡共享的调节元件。删除突触蛋白会破坏突触前囊泡簇的组织，使其边界难以确定。同时，可转运的囊泡比例增加，更多的囊泡被转运到轴突。重要的是，在突触蛋白敲除小鼠的神经元中，休息池和循环池同样具有流动性。当突触蛋白存在时，特异性地限制静息池囊泡的移动，而不影响这些池之间囊泡的分裂。突触蛋白IIa是影响突触抑制的唯一同种异构体，它的特异性表达挽救了基因敲除表型。综上所述，我们的研究结果表明突触蛋白对于维持突触囊泡簇的完整性至关重要，并且它有助于调节终端之间囊泡的共享。
Presynaptic terminals are specialized sites for information transmission where vesicles fuse with the plasma membrane and are locally recycled. Recent work has extended this classical view, with the observation that a subset of functional vesicles is dynamically shared between adjacent terminals by lateral axonal transport. Conceptually, such transport would be expected to disrupt vesicle retention around the active zone, yet terminals are characterized by a high-density vesicle cluster suggesting that counteracting stabilizing mechanisms must operate against this tendency. The synapsins are a family of proteins that associate with synaptic vesicles and determine vesicle numbers at the terminal, but their specific function remains controversial. Here, using multiple quantitative fluorescence-based approaches and electron microscopy, we show that synapsin is instrumental for resisting vesicle dispersion and serves as a regulatory element for controlling lateral vesicle sharing between synapses. Deleting synapsin disrupts the organization of presynaptic vesicle clusters, making their boundaries hard to define. Concurrently, the fraction of vesicles amenable to transport is increased, and more vesicles are translocated to the axon. Importantly, in neurons from synapsin knockout mice the resting and recycling pools are equally mobile. Synapsin, when present, specifically restricts the mobility of resting pool vesicles without affecting the division of vesicles between these pools. Specific expression of synapsin IIa, the sole isoform affecting synaptic depression, rescues the knockout phenotype. Taken together, our results show that synapsin is pivotal for maintaining synaptic vesicle cluster integrity and that it contributes to the regulated sharing of vesicles between terminals.