Connecting the dots between G proteins, G protein coupled receptors, and neuronal nicotinic acetylcholine receptors (Comment on DOI 10.1002/bies.201300082).
Connecting the dots between G proteins, G protein coupled receptors, and neuronal nicotinic acetylcholine receptors (Comment on DOI 10.1002/bies.201300082).
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连接 G 蛋白、G 蛋白偶联受体和神经元烟碱乙酰胆碱受体之间的点（DOI 10.1002/bies.201300082 的评论）。
DOI：
10.1002/bies.201300148
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Hawrot,Edward
中科院分区：
文献类型：
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作者：
Hawrot,Edward
Kabbani等人[1]在本卷假设部分的文章中，提出了异源三聚体G蛋白(鸟苷核苷酸结合蛋白)、G蛋白偶联受体(GPCRs)和神经元烟碱型乙酰胆碱受体之间功能上重要的相互作用的强有力的案例。他们从一系列令人印象深刻的相关文献中收集信息，并将其与对受体结构的新分析结合起来，以产生一个可检验的假说，即神经元烟碱型乙酰胆碱受体主要细胞内环中的某些氨基酸形成G蛋白的结合部位。为什么这会引起人们的兴趣？首先，GPCRs为大量药物提供了重要的靶点，并与许多生理功能有关。同样，烟碱型乙酰胆碱受体(NAChRs)作为神经递质受体家族的代表已被广泛研究，这些受体通过其固有的配体门控离子通道发挥其主要作用。这些不同的受体家族中的一些成员是否可以通过G蛋白作为细胞内信使的蛋白质相互作用网络联系在一起？烟碱型乙酰胆碱受体和G蛋白之间相互作用的一些最有力的证据来自对由α7亚基组成的神经元型烟碱型乙酰胆碱受体的有限数量的功能和蛋白质组学研究。Alpha7 nAChR被认为在许多方面都是祖先，因为它的存在延伸到了广泛的无脊椎动物物种。系统发育分析支持这一观点，也支持这一事实，即α7 nAChR烟碱型乙酰胆碱受体是一个只由一种亚基组成的五聚体，即α7，与所有其他nAChR不同，α7亚基显然是通过基因复制和选择进化而来的，它是由包括人类在内的哺乳动物中大约12个不同亚基形成的异源五聚体阵列。值得注意的是，近年来，Alpha7亚单位也因其在包括小鼠巨噬细胞在内的各种非神经性组织和细胞类型中的表达而引起了人们的注意，在这些细胞中，Alpha7亚单位nAChR参与了通过刺激迷走神经来调节炎症[2]。在许多情况下，非神经元组织中含有nAChRs的α7亚单位是否具有配体门控离子通道的功能尚不清楚，因为即使在神经元中证明α7介导的离子通量在技术上也是非常具有挑战性的。
Kabbani et al.[1] in their article in the Hypothesis section of the present volume, present a strong case for functionally important interactions between heterotrimeric G proteins (guanosine nucleotide-binding proteins), G protein coupled receptors (GPCRs), and neuronal nicotinic acetylcholine receptors. They compile information from an impressive array of relevant findings in the literature and couple this with a new analysis of receptor structure to generate a testable hypothesis that certain amino acids in the major intracellular loop of neuronal nicotinic acetylcholine receptors form the binding site for G proteins. Why is this of interest? For one, the GPCRs provide important targets for a large number of drugs and have been implicated in numerous physiological functions. Similarly, nicotinic acetylcholine receptors (nAChRs) have been widely studied as representative of the family of neurotransmitter receptors that produce their major effects through their intrinsic ligandgated ion channels. Could some members of these disparate receptor families be linked through a network of protein interactions involving G proteins as intracellular messengers?Some of the strongest evidence for an interaction between nicotinic acetylcholine receptors and G proteins comes from a limited number of functional and proteomic studies of the neuronal nicotinic acetylcholine receptor made up of the alpha7 subunit. The alpha7 nAChR is considered to be ancestral in many respects as its presence extends to a wide number of invertebrate species. Phylogenetic analysis supports this view as well as the fact that the alpha7 nAChR nicotinic acetylcholine receptor is a pentamer consisting of only one type of subunit, ie, alpha7, unlike all other nAChRs, which have apparently evolved through gene duplication and selection as a heterogenous array of heteromeric pentamers formed from about a dozen different subunits in mammals including humans. Notably, the alpha7 subunit has also drawn attention in recent years for its expression in a variety of non-neuronal tissues and cell types including murine macrophages where the alpha7 subunit nAChR has been implicated in the regulation of inflammation through stimulation of the vagus nerve [2]. In many cases, it is unclear whether the alpha7 subunit containing nAChRs located in non-neuronal tissue function as ligand-gated ion channels, as it can be very technically challenging to demonstrate alpha7-mediated ion flux even in neurons.