Muscarinic receptor oligomerization.
Muscarinic receptor oligomerization.
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DOI：
10.1016/j.neuropharm.2017.11.023
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发表时间：
2018-07-01
影响因子：
4.7
通讯作者：
Milligan G
中科院分区：
文献类型：
--
作者：
Marsango S;Ward RJ;Alvarez-Curto E;Milligan G
G 蛋白偶联受体 (GPCR) 被经典地描述为单体实体，通过以 1:1 的化学计量比与配体和下游信号蛋白结合而发挥作用。然而，近年来，越来越多的研究支持这些受体可以相互作用形成二聚体和更高阶寡聚体的假设，尽管这些相互作用的分子基础、整体四元排列和 GPCR 寡聚化的功能重要性仍然是人们强烈猜测的话题。毒蕈碱乙酰胆碱受体属于 GPCR 家族的 A 类。每种毒蕈碱受体亚型在中枢和周围神经系统中都有其特定的分布。在中枢神经系统中，毒蕈碱受体调节多种感觉、认知和运动功能，而在周围神经系统中，它们参与调节心率、刺激腺体分泌和平滑肌收缩。毒蕈碱乙酰胆碱受体长期以来一直被用作研究 GPCR 结构和功能的模型，并使用多种方法解决 GPCR 二聚化的问题。在这篇综述中，通过讨论从使用更传统的生化方法获得的初步结果到使用更现代的生物物理技术产生的结果的工作，总结了有关各种毒蕈碱乙酰胆碱受体四级排列的流行知识。本文是题为“毒蕈碱受体的神经药理学”特刊的一部分。毒蕈碱乙酰胆碱受体是在神经系统中表达的 GPCR。这些受体可以作为单体发挥作用，也可以形成二聚体和寡聚体。人们采用了多种方法来研究它们的四级结构。本文讨论了 30 多年工作取得的主要成果。
G protein-coupled receptors (GPCRs) have been classically described as monomeric entities that function by binding in a 1:1 stoichiometric ratio to both ligand and downstream signalling proteins. However, in recent years, a growing number of studies has supported the hypothesis that these receptors can interact to form dimers and higher order oligomers although the molecular basis for these interactions, the overall quaternary arrangements and the functional importance of GPCR oligomerization remain topics of intense speculation. Muscarinic acetylcholine receptors belong to class A of the GPCR family. Each muscarinic receptor subtype has its own particular distribution throughout the central and peripheral nervous systems. In the central nervous system, muscarinic receptors regulate several sensory, cognitive, and motor functions while, in the peripheral nervous system, they are involved in the regulation of heart rate, stimulation of glandular secretion and smooth muscle contraction. Muscarinic acetylcholine receptors have long been used as a model for the study of GPCR structure and function and to address aspects of GPCR dimerization using a broad range of approaches. In this review, the prevailing knowledge regarding the quaternary arrangement for the various muscarinic acetylcholine receptors has been summarized by discussing work ranging from initial results obtained using more traditional biochemical approaches to those generated with more modern biophysical techniques. This article is part of the Special Issue entitled ‘Neuropharmacology on Muscarinic Receptors’. Muscarinic acetylcholine receptors are GPCRs expressed in the nervous systems. These receptors can function as monomers and also form dimers and oligomers. A broad range of approaches have been employed to study their quaternary structure. The main outcomes obtained from over 30 years of work are discussed here.
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DOI：
10.1074/jbc.m116.754887
发表时间：
2016-12-30
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Alvarez-Curto E;Inoue A;Jenkins L;Raihan SZ;Prihandoko R;Tobin AB;Milligan G
通讯作者：
Milligan G
影响因子：
8.8
作者：
Felce JH;Latty SL;Knox RG;Mattick SR;Lui Y;Lee SF;Klenerman D;Davis SJ
通讯作者：
Davis SJ
影响因子：
4.8
作者：
Alvarez-Curto, Elisa;Ward, Richard J.;Milligan, Graeme
通讯作者：
Milligan, Graeme
影响因子：
3.4
作者：
Godin, Antoine G.;Rappaz, Benjamin;Wisemant, Paul W.
通讯作者：
Wisemant, Paul W.
DOI：
10.1074/jbc.m115.649079
发表时间：
2015-06-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Aslanoglou D;Alvarez-Curto E;Marsango S;Milligan G
通讯作者：
Milligan G