ORGANIZATION OF PRESYNAPTIC ACTIVE ZONE BASED ON TOMOGRAPHIC RECONSTRUCTION

基于断层重建的突触前活动区组织

• 批准号: 7957647
• 负责人: Yishi Jin
• 金额: $ 4.68万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-15 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957647
• 关键词: Appearance; Caenorhabditis elegans; Complex; Computer Retrieval of Information on Scientific Projects Database; Diffuse; Docking; Exhibits; Funding; Grant; Image Analysis; Institution; Molecular; Mutation; Presynaptic Terminals; Proteins; Registries; Research; Research Personnel; Resources; Screening procedure; Source; Synapses; Synaptic Vesicles; United States National Institutes of Health; base; gain of function mutation; insight; mutant; postsynaptic; presynaptic; reconstruction

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. The active zones at the presynaptic terminals are located at the center of the synaptic vesicle exocytic zone, promote synaptic vesicles docking, and provide the precise registry between pre- and postsynaptic specializations. Active zones display morphologically distinct ultrastructures. By screening for C. elegans mutants with altered synaptic vesicles distribution, we discovered that the conserved protein SYD-2 is a key regulator of active zone assembly. In syd-2 lost-of-function mutants, active zones exhibit a fragmented appearance, causing diffused localization of synaptic vesicles. Recently, we uncovered an unusual syd-2 gain-of-function mutation that is able to promote synapse assembly in the absence of several upstream regulators. Using this mutation, we have dissected the complex interactions among active zone proteins. This study provides insight into the molecular network of presynaptic active zone assembly.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 突触前末梢的活性区位于突触小泡胞吐区的中心，促进突触小泡对接，并提供突触前和突触后特化之间的精确注册。活性区显示出形态上不同的超微结构。通过筛选突触小泡分布改变的线虫突变体，我们发现保守蛋白 SYD-2 是活性区组装的关键调节因子。在 syd-2 功能丧失突变体中，活性区表现出碎片化的外观，导致突触小泡的弥散定位。最近，我们发现了一种不寻常的 syd-2 功能获得突变，它能够在缺乏几个上游调节因子的情况下促进突触组装。利用这种突变，我们剖析了活性区蛋白之间复杂的相互作用。这项研究提供了对突触前活性区组装分子网络的深入了解。