Lipovsek Marcela, Marcovich Irina, Elgoyhen Ana Belén
Ear Institute, Faculty of Brain Sciences, University College London, London, United Kingdom.
Departments of Otolaryngology & Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.
Front Cell Neurosci. 2021 Nov 15;15:785265. doi: 10.3389/fncel.2021.785265. eCollection 2021.
Nicotinic acetylcholine receptors (nAChRs) are a subfamily of pentameric ligand-gated ion channels with members identified in most eumetazoan clades. In vertebrates, they are divided into three subgroups, according to their main tissue of expression: neuronal, muscle and hair cell nAChRs. Each receptor subtype is composed of different subunits, encoded by paralogous genes. The latest to be identified are the α9 and α10 subunits, expressed in the mechanosensory hair cells of the inner ear and the lateral line, where they mediate efferent modulation. α9α10 nAChRs are the most divergent amongst all nicotinic receptors, showing marked differences in their degree of sequence conservation, their expression pattern, their subunit co-assembly rules and, most importantly, their functional properties. Here, we review recent advances in the understanding of the structure and evolution of nAChRs. We discuss the functional consequences of sequence divergence and conservation, with special emphasis on the hair cell α9α10 receptor, a seemingly distant cousin of neuronal and muscle nicotinic receptors. Finally, we highlight potential links between the evolution of the octavolateral system and the extreme divergence of vertebrate α9α10 receptors.
烟碱型乙酰胆碱受体（nAChRs）是五聚体配体门控离子通道的一个亚家族，在大多数真后生动物进化枝中都有其成员被鉴定出来。在脊椎动物中，根据其主要表达组织，它们被分为三个亚组：神经元型、肌肉型和毛细胞型nAChRs。每个受体亚型由不同的亚基组成，这些亚基由同源基因编码。最新被鉴定出来的是α9和α10亚基，它们在内耳和侧线的机械感觉毛细胞中表达，在那里介导传出调制。α9α10 nAChRs是所有烟碱型受体中差异最大的，在序列保守程度、表达模式、亚基共组装规则，以及最重要的功能特性方面都表现出显著差异。在这里，我们综述了对nAChRs结构和进化理解的最新进展。我们讨论了序列差异和保守性的功能后果，特别强调了毛细胞α9α10受体，它似乎是神经元型和肌肉型烟碱型受体的远亲。最后，我们强调了八侧线系统的进化与脊椎动物α9α10受体的极端差异之间的潜在联系。
