ORGANIZATION OF PRESYNAPTIC ACTIVE ZONE BASED ON TOMOGRAPHIC RECONSTRUCTION

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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 中心，不一定是研究者的机构。 突触前终末的活性区位于突触囊泡胞吐区的中心，促进突触囊泡对接，并提供突触前和突触后特化之间的精确登记。活动区显示形态学上不同的超微结构。通过筛选C.通过研究突触囊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丧失功能的突变体中，活性区表现出碎片化的外观，导致突触囊泡的扩散定位。最近，我们发现了一种不寻常的syd-2功能获得性突变，它能够在缺乏几种上游调节因子的情况下促进突触组装。利用这种突变，我们解剖了活性区蛋白之间的复杂相互作用。这项研究提供了深入了解突触前活动区组装的分子网络。

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.