MOLECULAR MECHANISMS OF NEUROTRANSMITTER SECRETION

神经递质分泌的分子机制

• 批准号: 2698826
• 负责人: ANDREW J BEAN
• 金额: $ 17.02万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2698826
• 关键词: adenosinetriphosphatase; calcium flux; enzyme activity; intermolecular interaction; intracellular transport; membrane activity; neurotransmitter transport; protein binding; protein localization; synaptic vesicles; tissue /cell culture

DESCRIPTION (Adapted from applicant's abstract): Calcium-dependent secretion constitutes the primary mode of communication in the nervous system. The long-term goal of this research is an understanding of the molecular events underlying this process. Modifications in neurotransmission affect many critical processes such as learning and memory, and perturbations in this system are thought to be involved in the etiology of several affective disorders. While significant progress has been made in this area over the last few years, many critical issues remain regarding the mechanisms that underlie and modulate secretion. The intracellular trafficking of neurotransmitter-containing vesicles is proposed to be mediated by the formation and dissolution of specific protein complexes composed of elements residing on vesicular and plasma membranes as well as cytoplasmic components. Hrs-2 is an ATPase that interacts with SNAP-25, plasma membrane-associated protein known to be critical for secretion. Hrs-2 is regulated by divalent cations known to influence secretion and inhibits secretion from permeabilized cells. We propose to further characterize the mechanism by which hrs-2 acts in the secretory process. A complementary, multi-faceted approach is being taken which includes: (1) analyzing hrs-2 protein interactions and their regulation, (2) defining the distribution and regulation of the membrane association of hrs-2, (3) examining the regulation of hrs-2 ATPase activity, and (4) characterizing the molecular mechanisms by which hrs-2 inhibits secretion.

描述（改编自申请人的摘要）：依赖钙 分泌构成紧张的主要交流方式 系统。 这项研究的长期目标是了解 该过程的分子事件。 修改 神经传递会影响许多关键过程，例如学习和 人们认为记忆和该系统中的扰动涉及 几种情感障碍的病因。 虽然取得了重大进展 在过去几年中在该领域制作，仍然存在许多关键问题 关于基础和调节分泌的机制。 这 含神经递质囊泡的细胞内运输是 建议通过特定蛋白的形成和溶解来介导 由位于囊泡和质膜上的元素组成的复合物作为 以及细胞质成分。 HRS-2是与与 SNAP-25，质膜相关蛋白已知至关重要 分泌。 HRS-2受已知会影响的二价阳离子的调节 分泌并抑制透化细胞的分泌。 我们建议 进一步表征了HRS-2在分泌中作用的机制 过程。 正在采取一种互补的，多方面的方法 包括：（1）分析HRS-2蛋白相互作用及其调节， （2）定义膜关联的分布和调节 HRS-2，（3）检查HRS-2 ATPase活性的调节，（4） 表征HRS-2抑制分泌的分子机制。