Molecular Mechanisms of Neurotransmitter Secretion

神经递质分泌的分子机制

• 批准号: 6528517
• 负责人: ANDREW J BEAN
• 金额: $ 29.8万
• 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 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6528517
• 关键词: adenosinetriphosphatase; calcium flux; endocytosis; intermolecular interaction; intracellular membranes; membrane activity; neurotransmitter transport; protein structure function; synaptic vesicles; tissue /cell culture; vesicle /vacuole

DESCRIPTION (provided by applicant): The calcium-dependent fusion of neurotransmitter-containing synaptic vesicles with the plasma membrane, and the rapid retrieval of the vesicular membrane for reuse, underlies the efficiency and regulation of synaptic transmission. Although synaptic transmission is a specialized case of vesicular trafficking to the plasma membrane, it is representative of the cyclical process of vesicle trafficking that allows the placement and removal of proteins and lipids onto the plasma membrane. For example, high-affinity receptors are added to the plasma membrane to enable transduction of various signals and they are internalized for degradation or reuse, a process that alters their signaling. The control of receptor signaling is critical for many processes such as synaptic transmission, cell growth, and cellular differentiation. Cells require endocytosis not only for the uptake of essential nutrients from the extracellular environment but also to retrieve proteins and lipids that are added to the plasma membrane during fusion of regulated and constitutive secretory vesicles. Hrs-2 is a protein ATPase that has been implicated in vesicular trafficking by virtue of functional interactions with proteins known to be essential for both exocytosis and endocytosis. Our preliminary data suggest a principal role for hrs-2 in endocytosis because it is localized primarily on endosomes, has interactions with proteins critical for endocytosis, is homologous to a yeast protein required for endosomal protein trafficking, affects receptor mediated endocytosis, and inhibits endosome fusion. Understanding the role of hrs-2 in the molecular mechanisms of endocytosis is the subject of the proposed studies that are outlined in the following Specific Aims: 1. To characterize the interactions of hrs-2 with endocytic trafficking proteins. 2. To examine the intrinsic biochemical/biophysical properties of hrs-2. 3. To determine the cellular/molecular role of hrs-2 in specific steps of endocytic trafficking.

描述（由申请人提供）： 含钙的神经递质突触囊泡的钙依赖性融合 与质膜和水泡膜快速检索 重复使用，是突触传播的效率和调节的基础。 尽管突触传播是囊泡贩运的专业案例 对于质膜，它代表了囊泡的周期性过程 贩运允许将蛋白质和脂质放置和去除 质膜。例如，将高亲和力受体添加到 质膜可实现各种信号，它们是 内部化以降解或重用，这是一个改变其信号的过程。 受体信号传导的控制对于许多过程，例如 突触传递，细胞生长和细胞分化。 细胞不仅需要内吞作用 细胞外环境，但也要检索蛋白质和脂质 在调节和本构融合过程中添加到质膜中 分泌囊泡。 HRS-2是一种与 通过与已知蛋白质的功能相互作用，囊泡运输 对于胞吐作用和内吞作用都是必不可少的。我们的初步数据 提出HRS-2在内吞作用中的主要作用，因为它是局部的 主要是在内体上，与至关重要的蛋白质相互作用 内吞作用，与内体蛋白所需的酵母蛋白同源 贩运，影响受体介导的内吞作用并抑制内体 融合。了解HRS-2在分子机制中的作用 内吞作用是拟议研究的主题 遵循特定目的： 1。表征HRS-2与内吞交易的相互作用 蛋白质。 2。检查HRS-2的内在生化/生物物理特性。 3。确定HRS-2在特定步骤中的细胞/分子作用 内吞贩运。