MOLECULAR MECHANISMS OF VESICULAR GLUTAMATE TRANSPORT

囊泡谷氨酸转运的分子机制

• 批准号: 7716141
• 负责人: RICHARD J REIMER
• 金额: $ 2.96万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716141
• 关键词: Address; Brain; Cell Communication; Cells; Chloride Channels; Computer Retrieval of Information on Scientific Projects Database; Computer information processing; Data; Funding; Glutamates; Goals; Grant; Institution; Lead; Molecular; Nature; Neuronal Injury; Neurons; Neurotransmitters; Play; Process; Proteins; Regulation; Research; Research Personnel; Resources; Role; Source; Structure; Synaptic Transmission; Synaptic Vesicles; United States National Institutes of Health; Vesicle; excitotoxicity; improved; inorganic phosphate; insight; protein function; vesicular glutamate transporter 1

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 broad long-term goal of this proposal is to define mechanisms involved in the regulation of information processing in the brain and how these mechanisms may impact on neuronal injury. Synaptic transmission, the major neuron specific mechanism for cell-to-cell communication, requires the concentration of neurotransmitters into synaptic vesicles to facilitate their rapid and precise release. Recently, the proteins responsible for the storage of the excitatory neurotransmitter glutamate in synaptic vesicles have been identified. However, the basic mechanisms by which these proteins (VGLUT1 and VGLUT2) function remain undetermined. Data suggests that VGLUT1 may also transport phosphate and function as a chloride channel. Since these additional functions will influence vesicular glutamate storage, it is important to clearly characterize the nature of the role that VGLUT1 plays in these processes. Three Aims are proposed to address these issues. The first Aim of this proposal is to define mechanism by which VGLUT1 catalyzes the accumulation of glutamate in synaptic vesicles. The second Aim is to determine if, in addition to transporting glutamate into vesicles, VGLUT1 also functions as a phosphate transport or chloride channel. The third Aim is to determine the secondary structure of VGLUT1 and the relationship of the structure to the functions of the protein. Progress in these Aims will lead to an improved understanding of the underlying molecular mechanisms of vesicular glutamate transport and insight into the role of VGLUT1 in vesicular storage of glutamate, synaptic transmission and excitotoxicity.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该提案的广泛长期目标是定义涉及大脑信息处理调节的机制以及这些机制如何影响神经元损伤。突触传递是细胞间通讯的主要神经元特异性机制，需要将神经递质集中到突触小泡中，以促进其快速、精确的释放。最近，已鉴定出负责在突触小泡中储存兴奋性神经递质谷氨酸的蛋白质。然而，这些蛋白质（VGLUT1 和 VGLUT2）发挥作用的基本机制仍未确定。数据表明 VGLUT1 还可能转运磷酸盐并发挥氯离子通道的作用。由于这些附加功能将影响囊泡谷氨酸储存，因此清楚地表征 VGLUT1 在这些过程中所发挥的作用的性质非常重要。提出了三个目标来解决这些问题。该提案的第一个目的是定义 VGLUT1 催化突触小泡中谷氨酸积累的机制。第二个目标是确定除了将谷氨酸转运到囊泡之外，VGLUT1 是否还具有磷酸盐转运或氯离子通道的功能。第三个目的是确定VGLUT1的二级结构以及该结构与蛋白质功能的关系。这些目标的进展将有助于更好地理解囊泡谷氨酸转运的潜在分子机制，并深入了解 VGLUT1 在囊泡谷氨酸储存、突触传递和兴奋性毒性中的作用。