Evolution and cell biology of dopamine receptors in vertebrates
Evolution and cell biology of dopamine receptors in vertebrates
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DOI：
10.1016/s0248-4900(03)00089-3
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发表时间：
2003-10-01
影响因子：
2.7
通讯作者：
Vernier, P
中科院分区：
文献类型：
--
作者：
Callier, S;Snapyan, M;Vernier, P
多巴胺是神经系统的主要调节性神经递质之一，通过两类G蛋白偶联受体D-1和D-2作用于靶细胞。这两类多巴胺受体具有不同的结构，与不同的调节伙伴(包括异源三聚体G蛋白)相互作用，因此具有独立的进化起源。在脊椎动物中，这些受体类别中的每一个都包括几个亚型，在脊椎动物进化的早期，由两个基因复制步骤产生。在D-1受体亚型中，D-1A、D-1B、D-1C和D-1D亚型；在D-2受体亚型中，D-2、D-3和D-4受体亚型在大多数脊椎动物中都是保守的。这种保守是由每个受体亚型获得少量特定属性推动的，这些属性是为脊椎动物的适应目的而选择的。在这些特性中，对多巴胺、天然配体的亲和力、内在受体活性和激动剂诱导的脱敏作用清楚地区分了受体亚型。此外，每个多巴胺受体亚型都被定位到神经元网络中的特定位置，尽管缺乏关于几个受体亚型的详细信息。受体在神经元不同亚细胞位置的定位也可能因亚型不同而不同，从而导致调节细胞信号传递的不同方式。未来对多巴胺及其受体的研究面临的一个挑战是确定蛋白质伙伴的性质以及将受体定位到神经细胞膜的分子机制。在这方面，我们采取的进化方法表明，由于基因复制，神经元中多巴胺受体的紧密组织存在合理程度的自由。这种多巴胺系统的“进化性”有助于脊椎动物适应几乎所有可能的环境。(C)2003年版《爱思唯尔科学与医学》。版权所有。
Dopamine, one of main modulatory neurotransmitters of the nervous system acts on target cells through two classes of G protein-coupled receptors, D-1 and D-2 The two dopamine receptor classes display different structures, interact with different regulatory partners (including heterotrimeric G proteins) and, accordingly, have independent evolutionary origins. In vertebrates, each of these receptor classes comprises several subtypes, generated by two steps of gene duplications, early in vertebrate evolution. In the D-1 receptor class, the D-1A, D-1B, D-1C and D-1D subtypes, and in the D-2 class, the D-2, D-3 et D-4 receptor subtypes have been conserved in most vertebrate groups. This conservation has been driven by the acquisition, by each receptor subtype, of a small number of specific properties, which were selected for adaptive purpose in vertebrates. Among these properties, affinity for dopamine, the natural ligand, intrinsic receptor activity, and agonist-induced desensitization clearly distinguish the receptor subtypes. In addition, each dopamine receptor subtype is addressed to a specific location within neuronal networks, although detailed information is lacking for several receptor subtypes. Receptors localization at diverse subcellular places in neurons may also differ from one subtype to another, resulting in different ways of regulating cell signalisation. One challenge for future research on dopamine and its receptors would be to identify the nature of the protein partners and the molecular mechanisms involved in localizing receptors to the neuronal plasma membrane. In this respect, the evolutionary approach we have undertaken suggests that, due to gene duplications, a reasonable degree of freedom exists in the tight organisation of dopamine receptors in neurons. This "evolvability" of dopamine systems has been instrumental to adapt the vertebrate species to nearly all the possible environments. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.