TOMOGRAPHY OF ENDOCYTIC INTERMEDIATES IN NERVE TERMINALS

神经末梢内吞中间体的断层扫描

• 批准号: 8362536
• 负责人: Pietro De Camilli
• 金额: $ 1.06万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362536
• 关键词: 3-Dimensional; Cell membrane; Cell physiology; Cellular Structures; Clathrin; Complex; Dynamin I; Endocytosis; Funding; Grant; Guanosine; Knockout Mice; Mus; National Center for Research Resources; Nerve; Neurons; Principal Investigator; Reaction; Research; Research Infrastructure; Resources; Source; Stimulus; Synapses; Synaptic Vesicles; Tubular formation; United States National Institutes of Health; coated pit; cost; electron tomography; mutant; postnatal; tomography

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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 Dynamin 1是一种神经元特异性的三磷酸酶，认为这是突触囊泡内吞作用的裂变反应所必需的。出乎意料的是，缺乏动力蛋白1的小鼠能够形成功能突触，即使它们的产后生存力受到限制。然而，在自发网络活性期间，在Dynamin 1基因敲除小鼠的突触中观察到复杂的管状囊泡起伏。使用串行，电子断层扫描的3-D分析进一步表明，这些突变突触中积累的分支的肾小管膜膜起伏，并且由粘蛋白涂层的凹坑盖住。突触囊泡内吞作用在强大的外源刺激期间严重受损，但在终止刺激时有效恢复。因此，Dynamin 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性中需要动力蛋白1。