The Hair Cell α9α10 Nicotinic Acetylcholine Receptor: Odd Cousin in an Old Family

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 alpha 9 and alpha 10 subunits, expressed in the mechanosensory hair cells of the inner ear and the lateral line, where they mediate efferent modulation. alpha 9 alpha 10 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 alpha 9 alpha 10 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 alpha 9 alpha 10 receptors.

Automated summary

Nicotinic acetylcholine receptors (nAChRs) are a subfamily of ion channels with five subunits, found in most animal clades. They are divided into three subgroups based on tissue of expression: neuronal, muscle, and hair cells, with different subunits including the recently identified alpha 9 and alpha 10 subunits. The alpha 9 alpha 10 nAChRs show the most divergence among nicotinic receptors, with differences in sequence conservation, expression pattern, subunit co-assembly rules, and functional properties.