Distinct Evolutionary Trajectories of Neuronal and Hair Cell Nicotinic Acetylcholine Receptors
Distinct Evolutionary Trajectories of Neuronal and Hair Cell Nicotinic Acetylcholine Receptors
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DOI：
10.1093/molbev/msz290
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发表时间：
2019-04
影响因子：
10.7
通讯作者：
Irina Marcovich;Marcelo J. Moglie;A. E. C. Freixas;Anabella P. Trigila;L. F. Franchini;P. Plazas;M. Lipovsek;A. Elgoyhen
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文献类型：
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作者：
Irina Marcovich;Marcelo J. Moglie;A. E. C. Freixas;Anabella P. Trigila;L. F. Franchini;P. Plazas;M. Lipovsek;A. Elgoyhen
离子通道家族的扩展和修剪在神经系统的进化中起着至关重要的作用。值得注意的是，作为高度保守的脊椎动物补体，烟碱乙酰胆碱受体（nachr）在配体门控离子通道中是独一无二的，因为该家族的成员在神经系统、内耳毛细胞或神经肌肉连接处的非重叠区域的突触传递中具有不同的作用。在此，我们对脊椎动物nAChRs序列、单细胞表达模式和三种代表性四足动物受体的比较功能特性进行了全面分析。我们发现毛细胞nachr经历了与神经元受体不同的进化轨迹。这些很可能是由组件亚单位的不同共表达模式和共组装规则形成的。因此，神经元nachr表现出高度的编码序列保守性，这与更大的共表达差异和四足动物进化枝的功能特性保守性相结合。相比之下，毛细胞α9α10 nAChRs序列差异较大，共表达模式窄，功能特性在物种间差异较大。这些结果指出了基因家族中随机变化的不同底物，这些底物与nachr在突触传递中的分离作用有关。我们的工作利用脊椎动物烟碱乙酰胆碱受体（nAChRs）家族的几个特点来探索配体门控离子通道家族的进化轨迹。通过对nAChR亚基编码序列、单细胞表达模式和功能特性的全面比较分析，我们发现在神经系统中广泛表达的nAChR与在内耳中分离表达的nAChR之间存在着截然不同的进化历史。进化变化主要集中在前者的共表达和共组装模式与后者的编码序列的差异。这种多学科的方法提供了进一步的洞察进化过程，塑造了现存动物的神经和感觉系统。
The expansion and pruning of ion channel families has played a crucial role in the evolution of nervous systems. Remarkably, with a highly conserved vertebrate complement, nicotinic acetylcholine receptors (nAChRs) are unique among ligand-gated ion channels in that members of the family have distinct roles in synaptic transmission in non-overlapping domains, either in the nervous system, the inner ear hair cells or the neuromuscular junction. Here, we performed a comprehensive analysis of vertebrate nAChRs sequences, single cell expression patterns and comparative functional properties of receptors from three representative tetrapod species. We show that hair cell nAChRs underwent a distinct evolutionary trajectory to that of neuronal receptors. These were most likely shaped by different co-expression patterns and co-assembly rules of component subunits. Thus, neuronal nAChRs showed high degree of coding sequence conservation, coupled to greater co-expression variance and conservation of functional properties across tetrapod clades. In contrast, hair cell α9α10 nAChRs exhibited greater sequence divergence, narrow co-expression pattern and great variability of functional properties across species. These results point to differential substrates for random change within the family of gene paralogs that relate to the segregated roles of nAChRs in synaptic transmission. Significance statement Our work exploits several peculiarities of the family of vertebrate nicotinic acetylcholine receptors (nAChRs) to explore the evolutionary trajectories of a ligand-gated ion channel family. By performing a comprehensive comparative analysis of nAChR subunits coding sequences, single cell expression patterns and functional properties we found a contrasting evolutionary history between nAChRs with widespread expression in the nervous system compared to those with isolated expression in the inner ear. Evolutionary changes were focused on differences in co-expression and co-assembly patterns for the former and coding sequences in the latter. This multidisciplinary approach provides further insight into the evolutionary processes that shaped the nervous and sensory systems of extant animals.