Glutamate Delta-1 Receptor and Metabotropic Glutamate Receptor Interaction

谷氨酸 Delta-1 受体和代谢型谷氨酸受体相互作用

• 批准号: 1456818
• 负责人: Shashank Dravid
• 金额: $ 72.61万
• 依托单位: Creighton University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1456818&HistoricalAwards=false
• 关键词: Glutamate; Delta; Receptor; Metabotropic; Interaction

Neurons in the brain communicate with each other through proteins that are present on specialized structures called spines that extend out from the neuron cell membrane. During neuron activity, the number and shape of spines change. Understanding how these changes occur is important because the changes are associated with learning and memory. The PI will study one particular protein that is highly abundant in spines and known to be critical for learning. The goal of the project is to determine how this protein and the proteins that it interacts with control spine shape and number. Undergraduate and graduate students, including underrepresented minorities, will participate in the research. The PI will present seminars on this area of research to the Health Science-Multicultural and Community Affairs (HS-MACA) Postbaccalaureate Program that is offered at his institution.Glutamate delta-1 receptors are orphan receptors that, unlike other members of the ionotropic glutamate receptor family, do not function as typical ligand-gated ion channels. Understanding their mechanism of action is important because the receptors are crucial for normal dendritic spine pruning, associative and reversal learning, and execution of complex behaviors. This project will investigate the potential interaction of glutamate delta-1 receptor with metabotropic glutamate receptors, which are also enriched at glutamatergic synapses. The working hypothesis for the proposed studies is that the glutamate delta-1 receptor regulates downstream metabotropic glutamate receptor signaling, including the mammalian target of rapamycin (mTOR) pathway, which regulates spine morphology. A multidisciplinary approach will be carried out that will make use of genetic and pharmacological tools, functional assays, diolistic labeling, and three dimensional reconstruction techniques. Outcomes are directed at developing a mechanistic understanding of glutamatergic synapse structure and function in the central nervous system.

大脑中的神经元通过蛋白质相互交流，这些蛋白质存在于从神经元细胞膜延伸出来的称为棘的专门结构上。 在神经元活动期间，棘的数量和形状发生变化。 了解这些变化是如何发生的很重要，因为这些变化与学习和记忆有关。 PI将研究一种特殊的蛋白质，这种蛋白质在脊椎中非常丰富，并且已知对学习至关重要。 该项目的目标是确定这种蛋白质及其相互作用的蛋白质如何控制脊柱的形状和数量。 本科生和研究生，包括代表性不足的少数民族，将参与研究。 主要研究者将向其所在机构提供的健康科学-多元文化和社区事务（HS-MACA）学士后项目介绍这一研究领域的研讨会。谷氨酸δ-1受体是孤儿受体，与离子型谷氨酸受体家族的其他成员不同，它不具有典型的配体门控离子通道的功能。 了解它们的作用机制很重要，因为受体对于正常的树突棘修剪、联想和反向学习以及复杂行为的执行至关重要。本研究将探讨谷氨酸delta-1受体与代谢型谷氨酸受体的潜在相互作用，代谢型谷氨酸受体也富集在谷氨酸能突触中。拟议研究的工作假设是谷氨酸delta-1受体调节下游代谢型谷氨酸受体信号传导，包括调节棘形态的哺乳动物雷帕霉素靶蛋白（mTOR）通路。一个多学科的方法将进行，将利用遗传和药理学工具，功能测定，diolistic标签，和三维重建技术。 结果是针对发展一个机械的理解，在中枢神经系统的神经元突触的结构和功能。