Conformational mechanisms of mGluR gating and regulation

mGluR 门控和调节的构象机制

基本信息

  • 批准号:
    10298420
  • 负责人:
  • 金额:
    $ 40.13万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-07-15 至 2025-06-30
  • 项目状态:
    未结题

项目摘要

SUMMARY/ABSTRACT G-protein–coupled receptors (GPCRs), the largest class of membrane signaling proteins, respond to a wide array of extracellular stimuli to initiate intracellular signaling via G proteins and arrestins. Recent studies have provided snapshots of GPCR structures in distinct conformations and revealed that they are extremely dynamic. The conformational dynamics appear to be central to ligand recognition, activation and signaling. Membrane receptors have evolved to respond to precise spatio-temporal concentration profiles of extracellular ligands. In the nervous system, neurotransmitter receptors encounter a wide range of neurotransmitter concentrations and spatio-temporal profiles. Key factors are the small extracellular volume of the synaptic cleft, pumps and/or enzymes that remove neurotransmitter, and diffusion. Additionally, neurotransmitter receptors can be localized within the synapse both pre- and postsynaptically, as well as extrasynaptically where they can encounter neurotransmitter released either locally, which briefly reaches low millimolar levels within the cleft, and spillover from nearby synapses, which reaches lower concentrations. Metabotropic glutamate receptors (mGluRs) are found pre- and postsynaptically at excitatory glutamatergic synapses, as well as on glia and at inhibitory GABAergic presynaptic nerve terminals, meaning that they are activated by both high local concentrations near the site of release and spillover. mGluRs of various kinds can be found together in presynaptic nerve terminals, even when they are all coupled to the same G protein. And they can dimerize, generating hybrid or in some cases totally unique properties and pharmacological profiles. To understand what each mGluR subtype does and develop effective drugs to treat the neurological disorders in which they are implicated, we need to understand how they function and how they are regulated. Our goal here is to define the molecular mechanisms that set and regulate the functional properties of homo- and heteromeric mGluRs at synapses and put into place assays that can be used to screen modulation in the nervous system.
摘要/文摘

项目成果

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Ehud Isacoff其他文献

Ehud Isacoff的其他文献

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{{ truncateString('Ehud Isacoff', 18)}}的其他基金

Conformational mechanisms of mGluR gating and regulation
mGluR 门控和调节的构象机制
  • 批准号:
    10665636
  • 财政年份:
    2021
  • 资助金额:
    $ 40.13万
  • 项目类别:
Conformational mechanisms of mGluR gating and regulation
mGluR 门控和调节的构象机制
  • 批准号:
    10443878
  • 财政年份:
    2021
  • 资助金额:
    $ 40.13万
  • 项目类别:
Optical control of neuromodulatory GPCRs
神经调节 GPCR 的光学控制
  • 批准号:
    10012228
  • 财政年份:
    2020
  • 资助金额:
    $ 40.13万
  • 项目类别:
Synaptic to circuit homeostasis in the Drosophila locomotor system
果蝇运动系统中的突触与电路稳态
  • 批准号:
    10654556
  • 财政年份:
    2019
  • 资助金额:
    $ 40.13万
  • 项目类别:
Synaptic to circuit homeostasis in the Drosophila locomotor system
果蝇运动系统中的突触与电路稳态
  • 批准号:
    10438585
  • 财政年份:
    2019
  • 资助金额:
    $ 40.13万
  • 项目类别:
Synaptic to circuit homeostasis in the Drosophila locomotor system
果蝇运动系统中的突触与电路稳态
  • 批准号:
    10210452
  • 财政年份:
    2019
  • 资助金额:
    $ 40.13万
  • 项目类别:
Voltage Gating Mechanisms
电压门控机制
  • 批准号:
    9010555
  • 财政年份:
    2016
  • 资助金额:
    $ 40.13万
  • 项目类别:
Novel tools for cell-specific imaging of functional connectivity and circuit operations
用于功能连接和电路操作的细胞特异性成像的新工具
  • 批准号:
    9343283
  • 财政年份:
    2015
  • 资助金额:
    $ 40.13万
  • 项目类别:
Novel tools for cell-specific imaging of functional connectivity and circuit operations
用于功能连接和电路操作的细胞特异性成像的新工具
  • 批准号:
    9036880
  • 财政年份:
    2015
  • 资助金额:
    $ 40.13万
  • 项目类别:
Optical control of synaptic transmission for in vivo analysis of brain circuits and behavior
突触传递的光学控制用于脑回路和行为的体内分析
  • 批准号:
    8934227
  • 财政年份:
    2014
  • 资助金额:
    $ 40.13万
  • 项目类别:

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