Characterization of Neuroendocrine CGRP Receptors
神经内分泌 CGRP 受体的表征
基本信息
- 批准号:6863628
- 负责人:
- 金额:$ 29.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-01-01 至 2007-02-28
- 项目状态:已结题
- 来源:
- 关键词:3T3 cellsbiological signal transductioncalcitonin gene related peptidegene targetingimmunoprecipitationmembrane proteinsneuropeptide receptorprotein protein interactionprotein structure functionreceptor bindingreceptor couplingreceptor expressionreceptor sensitivitytransfectionyeast two hybrid system
项目摘要
DESCRIPTION (provided by applicant): We have discovered a 148 aa protein named calcitonin gene-related peptide (CGRP)-receptor component protein (RCP) that is required for G protein-coupled signal transduction at receptors for the neuropeptide CGRP. During the previous project period we determined that RCP works in conjunction with two other proteins to constitute a functional CGRP receptor: calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein (RAMP1). CRLR has the stereotypical 7-transmembrane topology of a G protein-coupled receptor, and requires RAMP1 for trafficking to the cell surface and for ligand specificity, and requires RCP for coupling to the cellular signal transduction pathway. CRLR did not function in antisense cell lines that inhibited RCP expression, and CRLR co-immunoprecipitated with RCP suggesting that the two proteins were together in complex. The specific hypotheses to be tested in this proposal are that a functional CGRP receptor is composed of at least three proteins: CRLR, RCP, and RAMP1, and that the accessory proteins RCP and RAMP1 can modulate CRLR function. The specific aims of this proposal are to: 1) determine the sites of interaction between RCP and CRLR required for a functional CGRP receptor, using yeast two-hybrid assay and cell culture, 2) determine if overexpression of RAMP1 or RCP can increase CGRP receptor function in cell culture, 3) determine if loss of RCP by homologous recombination has increased inhibitory effects on CGRP receptor function in cell culture, 4) identify the cellular environment that regulates the CGRP receptor complex, focusing on lipid rafts and their effect on receptor function and receptor distribution in the membrane.
Recent studies have found that in hypertension the vasculature is hyper-responsive to CGRP, suggesting regulation of CGRP receptor function. Thus, the role of RCP in regulating CGRP receptor function is important both for fundamental studies on G protein-mediated signal transduction in neuroendocrine cells, but also for future therapeutic strategies for vascular disorders.
描述(申请人提供):我们已经发现了一种名为降钙素基因相关肽(CGRP)-受体组件蛋白(RCP)的148氨基酸蛋白质,它是神经肽CGRP受体上G蛋白偶联信号转导所必需的。在之前的项目期间,我们确定了RCP与另外两种蛋白质共同作用,构成一个功能性的CGRP受体:降钙素受体样受体(CRLR)和受体活性修饰蛋白(RAMP1)。CRLR具有典型的G蛋白偶联受体的7-跨膜拓扑结构,需要RAMP1运输到细胞表面和配体特异性,并需要RCP偶联到细胞信号转导途径。CRLR在抑制RCP表达的反义细胞系中不起作用,CRLR与RCP免疫共沉淀,表明两种蛋白以复合体形式存在。在这一建议中需要检验的具体假设是,一个具有功能的CGRP受体至少由三个蛋白质组成:CRLR、RCP和RAMP1,辅助蛋白RCP和RAMP1可以调节CRLR的功能。该建议的具体目的是:1)利用酵母双杂交试验和细胞培养确定RCP与CRLR之间的相互作用部位;2)确定RAMP1或RCP的过表达是否能增加细胞培养中的CGRP受体功能;3)确定RCP因同源重组而丢失是否会增加对细胞培养中CGRP受体功能的抑制作用;4)确定调节CGRP受体复合体的细胞环境,重点关注脂筏及其对受体功能和膜上受体分布的影响。
最近的研究发现,高血压患者的血管系统对降钙素基因相关肽反应强烈,提示降钙素基因相关肽受体功能的调节。因此,RCP在调节CGRP受体功能中的作用不仅对G蛋白介导的神经内分泌细胞信号转导的基础研究,而且对未来血管疾病的治疗策略都具有重要意义。
项目成果
期刊论文数量(0)
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IAN M DICKERSON其他文献
IAN M DICKERSON的其他文献
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{{ truncateString('IAN M DICKERSON', 18)}}的其他基金
Enhanced CRISPR gene editing in pluripotent stem cells using carbon nanotube arrays
使用碳纳米管阵列增强多能干细胞中的 CRISPR 基因编辑
- 批准号:
10698269 - 财政年份:2023
- 资助金额:
$ 29.06万 - 项目类别:
Characterization of Neuroendocrine CGRP Receptors
神经内分泌 CGRP 受体的表征
- 批准号:
6578702 - 财政年份:1999
- 资助金额:
$ 29.06万 - 项目类别:
Characterization of Neuroendocrine CGRP Receptors
神经内分泌 CGRP 受体的表征
- 批准号:
7023795 - 财政年份:1999
- 资助金额:
$ 29.06万 - 项目类别:
Characterization of Neuroendocrine CGRP Receptors
神经内分泌 CGRP 受体的表征
- 批准号:
6785737 - 财政年份:1999
- 资助金额:
$ 29.06万 - 项目类别:
Characterization of Neuroendocrine CGRP Receptors
神经内分泌 CGRP 受体的表征
- 批准号:
6712079 - 财政年份:1999
- 资助金额:
$ 29.06万 - 项目类别:
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3036759 - 财政年份:1988
- 资助金额:
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