Direct Interaction Between GABA-A and GABA-B Receptors
GABA-A 和 GABA-B 受体之间的直接相互作用
基本信息
- 批准号:6596430
- 负责人:
- 金额:$ 25.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-02-01 至 2008-01-31
- 项目状态:已结题
- 来源:
- 关键词:G protein GABA receptor SDS polyacrylamide gel electrophoresis biological signal transduction brain cell line confocal scanning microscopy gamma aminobutyrate immunoprecipitation laboratory rat membrane channels neurotransmitters phosphorylation protein protein interaction receptor binding receptor expression transfection voltage /patch clamp western blottings
项目摘要
DESCRIPTION (provided by applicant): Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian brain. GABA exerts its physiological actions in the brain via the activation of two distinct types of receptor: GABA-A receptors, which are ligand-gated ion channels, and GABA-B receptors, which are G proteincoupled receptors. GABA-A and GABA-B receptors are known to exhibit forms of cross-talk and mutual regulation for which no mechanism has been defined. This project aims to study the importance of a novel and direct interaction found between the GABA-BR1 receptor and the gamma2 subunit of the GABA-A receptor. This physical association may provide a mechanism to allow for direct cross-talk between GABA-A and GABA-B receptors. The structural determinants and physiological significance of this interaction, however, are completely unknown at the present time. The specific regions of GABA-BR1 and the gamma2 subunit of the GABA-A receptor involved in mediating their interaction will be elucidated using a mutagenesis approach in combination with both co-immunoprecipitation and fusion protein pull-down studies. The effects of GABA-A receptor association on GABA-B receptor pharmacology will be studied in ligand binding assays, and GABA-A receptor modulation of GABA-B receptor signaling and internalization will also be analyzed. Furthermore, GABA-B receptor regulation of GABA-A receptor pharmacology, channel activity and phosphorylation will be examined, with an emphasis on determining the functional importance of the direct interaction between GABA-BR1 and the GABA-A receptor gamma2 subunit. These studies will shed new light on the regulation of cellular responses to GABA and the molecular basis for cross-talk between GABA-A and GABA-B receptors. Such information is critical for a comprehensive understanding of pharmaceuticals acting on GABA receptors. GABA-A receptors are the targets for such commonly prescribed therapeutic drugs as benzodiazepines and barbiturates, while the more recently-identified GABA-B receptors represent excellent potential targets for novel therapeutic drugs aimed at treating disorders such as schizophrenia, epilepsy, anxiety, chronic pain and depression.
描述(申请人提供):伽马氨基丁酸(GABA)是哺乳动物大脑中的主要抑制性神经递质。GABA通过激活两种不同类型的受体在大脑中发挥其生理作用:GABA-A受体是配体门控离子通道,GABA-B受体是G蛋白偶联受体。已知GABA-A和GABA-B受体表现出串扰和相互调节的形式,其机制尚未确定。本项目旨在研究在GABA-BR1受体和GABA-A受体的Gamma2亚单位之间发现一种新的直接相互作用的重要性。这种物理联系可能提供了一种机制,允许GABA-A和GABA-B受体之间的直接串扰。然而,这种相互作用的结构决定因素和生理意义目前完全未知。参与调节它们相互作用的GABA-BR1和GABA-A受体的Gamma2亚单位的特定区域将使用突变方法结合免疫共沉淀和融合蛋白下拉研究来阐明。通过配体结合实验研究GABA-A受体结合对GABA-B受体药理的影响,并分析GABA-A受体对GABA-B受体信号转导和内化的调节作用。此外,还将研究GABA-B受体对GABA-A受体药理、通道活性和磷酸化的调节,重点确定GABA-BR1和GABA-A受体Gamma2亚单位之间直接相互作用的功能重要性。这些研究将为调节细胞对GABA的反应以及GABA-A和GABA-B受体之间串扰的分子基础提供新的线索。这些信息对于全面了解作用于GABA受体的药物至关重要。GABA-A受体是苯二氮卓类和巴比妥类等常用治疗药物的靶标,而最近发现的GABA-B受体是旨在治疗精神分裂症、癫痫、焦虑、慢性疼痛和抑郁症等疾病的新型治疗药物的极佳潜在靶点。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Randy A. Hall其他文献
PDZ interactions between PHLPP phosphatases and the NHERF scaffold
PHLPP 磷酸酶和 NHERF 支架之间的 PDZ 相互作用
- DOI:
- 发表时间:
2012 - 期刊:
- 影响因子:0
- 作者:
M. Kunkel;E. Garcia;Randy A. Hall;A. Newton - 通讯作者:
A. Newton
Effects of cyclothiazide on synaptic responses in slices of adult and neonatal rat hippocampus.
环噻嗪对成年和新生大鼠海马切片突触反应的影响。
- DOI:
- 发表时间:
1994 - 期刊:
- 影响因子:1.7
- 作者:
John Larson;To;Randy A. Hall;Gary Lynch - 通讯作者:
Gary Lynch
Secタンパク質膜透過装置の活写にむけて
Sec蛋白膜渗透装置的实时成像
- DOI:
- 发表时间:
2014 - 期刊:
- 影响因子:0
- 作者:
Dan Zhu;Chenchen Li;Andrew M. Swanson;Rosa M. Villalba;Jidong Guo;Zhaobin Zhang;Shannon Matheny;Tatsuro Murakami;Jason R. Stephenson;Sarah Daniel;Masaki Fukata;Randy A. Hall;Jeffrey J. Olson;Gretchen N. Neigh;Yoland Smith;Donald G. Rainnie,;塚崎 智也,春山 隆充 ,菅野 泰功,田中 良樹 ,紺野 宏記 - 通讯作者:
塚崎 智也,春山 隆充 ,菅野 泰功,田中 良樹 ,紺野 宏記
Mini Review Adhesion G Protein-Coupled Receptors: Signaling, Pharmacology & Mechanisms of Activation
迷你回顾粘附 G 蛋白偶联受体:信号传导、药理学
- DOI:
- 发表时间:
2012 - 期刊:
- 影响因子:0
- 作者:
K. Paavola;Randy A. Hall - 通讯作者:
Randy A. Hall
Mice lacking full length Adgrb1 (Bai1) exhibit social deficitsem,/em increased seizure susceptibility, and altered brain development
缺乏全长 Adgrb1(Bai1)的小鼠表现出社交缺陷、癫痫易感性增加和大脑发育改变。
- DOI:
10.1016/j.expneurol.2022.113994 - 发表时间:
2022-05-01 - 期刊:
- 影响因子:4.200
- 作者:
Fu Hung Shiu;Jennifer C. Wong;Takahiro Yamamoto;Trisha Lala;Ryan H. Purcell;Sharon Owino;Dan Zhu;Erwin G. Van Meir;Randy A. Hall;Andrew Escayg - 通讯作者:
Andrew Escayg
Randy A. Hall的其他文献
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{{ truncateString('Randy A. Hall', 18)}}的其他基金
Disease-Associated Mutations and Ligand Activation of the Adhesion G Protein-Coupled Receptor ADGRB2
粘附 G 蛋白偶联受体 ADGRB2 的疾病相关突变和配体激活
- 批准号:
10811019 - 财政年份:2023
- 资助金额:
$ 25.27万 - 项目类别:
Control of Seizure and Migraine Susceptibility by GPR37L1
GPR37L1 控制癫痫和偏头痛易感性
- 批准号:
10449353 - 财政年份:2021
- 资助金额:
$ 25.27万 - 项目类别:
Control of Seizure and Migraine Susceptibility by GPR37L1
GPR37L1 控制癫痫和偏头痛易感性
- 批准号:
10279634 - 财政年份:2021
- 资助金额:
$ 25.27万 - 项目类别:
Control of Seizure and Migraine Susceptibility by GPR37L1
GPR37L1 控制癫痫和偏头痛易感性
- 批准号:
10651823 - 财政年份:2021
- 资助金额:
$ 25.27万 - 项目类别:
Activation and Regulation of the Synaptic Receptor BAI1
突触受体 BAI1 的激活和调节
- 批准号:
9900070 - 财政年份:2019
- 资助金额:
$ 25.27万 - 项目类别:
BAI2 mutation associated with a novel neurological disorder
BAI2 突变与新型神经系统疾病相关
- 批准号:
8877775 - 财政年份:2015
- 资助金额:
$ 25.27万 - 项目类别:
GPR37L1 mutation associated with a novel neurological disorder
GPR37L1 突变与新型神经系统疾病相关
- 批准号:
8871619 - 财政年份:2015
- 资助金额:
$ 25.27万 - 项目类别:
GPR37 & GPR37L1 signaling pathways promoting cell survival: relevance to stroke
探地雷达37
- 批准号:
8753503 - 财政年份:2014
- 资助金额:
$ 25.27万 - 项目类别:
GPR37 & GPR37L1 signaling pathways promoting cell survival: relevance to stroke
探地雷达37
- 批准号:
9464568 - 财政年份:2014
- 资助金额:
$ 25.27万 - 项目类别:
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