SYNAPTIC FUNCTION IN THE NEMATODE C. ELEGANS

描述(由申请人提供)： 神经递质通过突触小泡与质膜的融合从突触中释放出来。突触小泡必须首先停靠在质膜上，为融合做好准备，对钙做出反应并融合。突触囊泡的胞吐作用部分是由SNARE蛋白(Synaxin、Synaptobrevin和SNAP-25)、UNC-18和新的蛋白RIC-7介导的。我们将回答以下问题： UNC-18在胞吐作用中起什么作用？ 1.UNC-18是对接的直接调节器吗？ 2.拆解SNARE复合体是否需要UNC-18，以便这些蛋白能够在随后的几轮胞吐中发挥作用？ 3.UNC-18是否通过结合突触素抑制SNARE复合体的形成？ SNARE蛋白在胞吐作用中的作用是什么？ 4.对接是否需要语法标记？融合需要合成素吗？ 5.对接需要Synaptobrevin吗？是否需要与SYNAPTOAGMIN冗余地进行对接？融合需要突触素吗？突触蛋白是否需要额外的突触小泡才能提供给突触蛋白？ RIC-7在胞吐作用中起什么作用？ 6.RIC-7是突触所需的一种新蛋白。对接需要RIC-7吗？是否需要RIC-7来启动、钙感应或融合？ 这些研究将探索神经系统功能的分子机制。对突触的分子理解将为我们提供治疗阿尔茨海默病等神经退行性疾病、治疗拉斯穆森脑炎等自身免疫性疾病和神经系统遗传性疾病所需的知识基础。

DESCRIPTION (provided by applicant): Neurotransmitters are released from synapses by the fusion of synaptic vesicles with the plasma membrane. Synaptic vesicles must first dock to the plasma membrane, become primed for fusion, respond to calcium and fuse. Synaptic vesicle exocytosis is mediated in part by the SNARE proteins (syntaxin, synaptobrevin and SNAP-25), UNC-18 and the novel protein RIC-7. We will answer the following questions: What is the role of UNC-18 in exocytosis? 1. Is UNC-18 a direct regulator of docking? 2. Is UNC-18 required for the disassembly of the SNARE complex so that these proteins can function in subsequent rounds of exocytosis? 3. Does UNC-18 inhibit the formation of the SNARE complex by binding syntaxin? What is the role of SNARE proteins in exocytosis? 4. Is syntaxin required for docking? Is syntaxin required for fusion? 5. Is synaptobrevin required for docking? Is it required redundantly with synaptotagmin for docking? Is synaptobrevin required for fusion? Is it required redundantly with synaptotagmin to present synaptic vesicles to syntaxin? What is the role of RIC-7 in exocytosis? 6. RIC-7 is a novel protein required at the synapse. Is RIC-7 required for docking? Is RIC-7 required for priming, calcium sensing, or fusion? These studies will explore the molecular mechanisms of nervous system function. A molecular understanding of the synapse will provide us with the knowledge base that will be required to treat neurodegenerative disorders such as Alzheimer's Disease, to treat autoimmune diseases like Rasmussen's encephalitis, and genetic disorders of the nervous system.