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: 8169634
• 负责人: Yishi Jin
• 金额: $ 3.58万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169634
• 关键词: Appearance; Caenorhabditis elegans; Complex; Computer Retrieval of Information on Scientific Projects Database; Diffuse; Docking; Exhibits; Funding; Grant; 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.

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。 突触前终末的活动区位于突触小泡胞外区的中心，促进突触小泡的对接，并提供突触前和突触后特化之间的精确注册。活跃区在形态上表现出明显的超微结构。通过对突触小泡分布发生改变的线虫突变体的筛选，我们发现保守的蛋白SYD-2是活动区组装的关键调节因子。在Syd-2功能缺失突变体中，活动区呈现碎片化，导致突触小泡的弥漫性定位。最近，我们发现了一个不寻常的Syd-2功能获得突变，它能够在没有几个上游调控因子的情况下促进突触组装。利用这个突变，我们已经剖析了活动区蛋白之间的复杂相互作用。这项研究为了解突触前活动区组装的分子网络提供了洞察力。