TOMOGRAPHY OF ENDOCYTIC INTERMEDIATES IN NERVE TERMINALS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 发动蛋白1是一种神经元特异性鸟苷三磷酸酶，被认为是突触囊泡内吞作用的裂变反应所必需的。出乎意料的是，缺乏发动蛋白1的小鼠能够形成功能性突触，尽管它们出生后的生存能力有限。然而，在自发网络活动期间，在发动蛋白1的突触中观察到复杂的管状囊泡内陷敲除小鼠使用连续电子断层扫描的三维分析进一步显示，在这些突变突触中积累了分支管状质膜内陷，并且这些突触被网格蛋白包被的小凹覆盖。突触囊泡内吞作用在强烈的外源性刺激过程中严重受损，但刺激终止后有效地恢复。因此，发动蛋白1独立的机制可以支持有限的突触囊泡内吞作用，但是在高水平的神经元活动期间需要发动蛋白1。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dynamin 1 is a neuron-specific guanosine triphosphatase thought to be critically required for the fission reaction of synaptic vesicle endocytosis. Unexpectedly, mice lacking dynamin 1 were able to form functional synapses, even though their postnatal viability was limited. However, during spontaneous network activity, complex tubular vesicular invaginations were observed in synapses of dynamin 1knockout mice. A 3-D analysis using serial, electron tomography further revealed that branched, tubular plasma membrane invaginations accumulated in these mutant synapses, and these were capped by clathrin-coated pits. Synaptic vesicle endocytosis was severely impaired during strong exogenous stimulation but resumed efficiently when the stimulus was terminated. Thus, dynamin 1independent mechanisms can support limited synaptic vesicle endocytosis, but dynamin 1 is needed during high levels of neuronal activity.