TOMOGRAPHY OF ENDOCYTIC INTERMEDIATES IN NERVE TERMINALS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 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，在动力蛋白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进行的3D分析进一步揭示，分支的管状质膜内陷在这些突变突触中积累，并且这些突触被网格蛋白包被的小坑覆盖。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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.