Molecular and functional characterization of proteins interacting with the C-terminal domains of 5-HT2 receptors:: Emergence of 5-HT2 "Receptosomes"
Molecular and functional characterization of proteins interacting with the C-terminal domains of 5-HT2 receptors:: Emergence of 5-HT2 "Receptosomes"
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DOI：
10.1016/j.biolcel.2004.03.001
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发表时间：
2004-06-01
影响因子：
2.7
通讯作者：
Marin, P
中科院分区：
文献类型：
--
作者：
Gavarini, S;Bécamel, C;Marin, P
许多细胞功能是由多蛋白复合物完成的。过去五年的研究表明，许多G蛋白偶联受体（GPCR）的功能，不涉及G蛋白介导的蛋白质网络，与他们的细胞内结构域相互作用。本文综述了5-羟色胺激活的GPCR家族5-HT 2受体家族，该家族包括3个密切相关的亚型：5-HT 2A、5-HT 2B和5-HT 2c受体。这些受体仍然引起特别的兴趣，因为大量的精神活性药物，包括致幻剂、抗精神病药、抗焦虑药和抗抑郁药，至少部分地通过激活5-HT 2受体来介导它们的作用。最近的研究基于双杂交筛选、蛋白质组学、生物化学和细胞生物学方法，已经表明5-HT 2受体的C-末端结构域与细胞内蛋白质相互作用。迄今为止，与5-HT 2C受体的C-末端相关的蛋白质网络已被最广泛地表征，使用结合亲和层析、质谱和免疫印迹的蛋白质组学方法。它包括含有一个或几个PDZ结构域的支架蛋白、信号蛋白和细胞骨架蛋白。数据表明，与5-HT 2受体C-末端相互作用的蛋白质复合物紧密控制受体贩运和受体介导的信号传导也将进行审查。(C)2004年，Elsevier SAS。All rights reserved.
Many cellular functions are carried out by multiprotein complexes. The last five years of research have revealed that many G-protein coupled receptor (GPCR) functions that are not mediated by G proteins involve protein networks, which interact with their intracellular domains. This review focuses on one family of GPCRs activated by serotonin, the 5-HT2 receptor family, which comprises three closely related subtypes, the 5-HT2A, the 5-HT2B and the 5-HT2c receptors. These receptors still raise particular interest, because a large number of psychoactive drugs including hallucinogens, anti-psychotics, anxiolytics and anti-depressants, mediate their action, at least in part, through activation of 5-HT2 receptors. Recent studies based on two-hybrid screens, proteomic, biochemical and cell biology approaches, have shown that the C-terminal domains of 5-HT2 receptors interact with intracellular proteins. To date, the protein network associated with the C-terminus of the 5-HT2C receptor has been the most extensively characterized, using a proteomic approach combining affinity chromatography, mass spectrometry and immunoblotting. It includes scaffolding proteins containing one or several PDZ domains, signalling proteins and proteins of the cytoskeleton. Data indicating that the protein complexes interacting with 5-HT2 receptor C-termini tightly control receptor trafficking and receptor-mediated signalling will also be reviewed. (C) 2004 Elsevier SAS. All rights reserved.