TOMOGRAPHY OF ENDOCYTIC INTERMEDIATES IN NERVE TERMINALS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 Dynamin 1是一种神经元特异性的鸟苷三磷酸酶，被认为是突触囊泡内吞的裂变反应所必需的。出乎意料的是，缺乏Dynamin 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，在自发的网络活动中，在Dynamin 1基因敲除小鼠的突触中观察到复杂的管状囊泡内陷。用连续电子断层扫描进行的三维分析进一步显示，在这些突触中积累了分支的管状质膜内陷，这些突触被笼罩着网状蛋白的凹陷所覆盖。突触囊泡内吞作用在强外源性刺激时受到严重损害，但在刺激终止后有效地恢复。因此，Dynamin 1不依赖的机制可以支持有限的突触小泡内吞作用，但Dynamin 1在高水平的神经元活动中是必需的。

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.