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Molecular mechanisms of glutamate transporters

谷氨酸转运蛋白的分子机制

基本信息

批准号：
7739204
负责人：
Hans Peter Larsson
金额：
$ 6.24万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-03-01 至 2011-02-28
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Glutamate transporters remove glutamate from synapses to maintain an efficient synaptic communication between neurons and to prevent extracellular glutamate concentrations from reaching neuro-toxic levels. The long-term goal of this project is to understand the molecular mechanism of glutamate transporter. It is important to understand the molecular mechanism by which glutamate transporters achieved glutamate uptake, because this will lead to a better understanding of synaptic communication in the brain, as well as, lead to treatments to prevent neuronal death due to glutamate toxicity during, for example, ischemia. In addition, this study will provide essential structural and dynamical information about the glutamate transporters, an area of research in which there are only a few numbers of groups working. Our current knowledge of the structure and function of glutamate transporters is very limited. No structural model has yet been suggested that can explain how glutamate transporters accomplish glutamate uptake. We propose to use fluorescence and biochemical methods to elucidate the structure and function of glutamate transporters, using fluorescent and non-fluorescent cysteine reactive probes. These techniques allow us to obtain structural as well as dynamical information about the molecular mechanism of glutamate transporters. Our objective is to construct a structural model of glutamate transporters and to elucidate how changes in this structure lead to glutamate transport. The aims of the proposed project are: 1) To identify the domains of the glutamate transporters that undergo conformational changes during the transport cycle; and 2) To identify residues that undergo alternating access during glutamate transport.

描述(申请人提供)：谷氨酸转运体从突触中移除谷氨酸，以维持神经元之间有效的突触通讯，并防止细胞外谷氨酸浓度达到神经毒性水平。该项目的长期目标是了解谷氨酸转运体的分子机制。了解谷氨酸转运体实现谷氨酸摄取的分子机制是很重要的，因为这将有助于更好地了解大脑中的突触通讯，以及导致防止神经元死亡的治疗方法，例如在缺血期间由于谷氨酸毒性而导致的神经元死亡。此外，这项研究将提供有关谷氨酸转运体的基本结构和动力学信息，这是一个只有几个小组工作的研究领域。我们目前对谷氨酸转运体的结构和功能的了解非常有限。目前还没有结构模型可以解释谷氨酸转运体是如何完成谷氨酸摄取的。我们建议使用荧光和非荧光半胱氨酸反应探针，用荧光和生化方法来阐明谷氨酸转运体的结构和功能。这些技术使我们能够获得有关谷氨酸转运体分子机制的结构和动力学信息。我们的目标是构建谷氨酸转运体的结构模型，并阐明该结构的变化是如何导致谷氨酸转运体的。拟议项目的目的是：1)确定谷氨酸转运体在转运周期中发生构象变化的区域；以及2)确定在谷氨酸转运过程中经历交替访问的残基。