Prestin and the cholinergic receptor of hair cells: positively-selected proteins in mammals

Abstract

The hair cells of the vertebrate inner ear posses active mechanical processes to amplify their inputs. The stereocilia bundle of various vertebrate animals can produce active movements. Though standard stereocilia-based mechanisms to promote amplification persist in mammals, an additional radically different mechanism evolved: the so-called somatic electromotility which refers to the elongation/contraction of the outer hair cells' (OHC) cylindrical cell body in response to membrane voltage changes. Somatic electromotility in OHCs, as the basis for cochlear amplification, is a mammalian novelty and it is largely dependent upon the properties of the unique motor protein prestin. We review recent literature which has demonstrated that although the gene encoding prestin is present in all vertebrate species, mammalian prestin has been under positive selective pressure to acquire motor properties, probably rendering it fit to serve somatic motility in outer hair cells. Moreover, we discuss data which indicates that a modified α10 nicotinic cholinergic receptor subunit has co-evolved in mammals, most likely to give the auditory feedback system the capability to control somatic electromotility.

Figure 1

Predicted secondary structure and topology of human prestin based on the model previously described by Zheng et al. (2001, 2005, 2006). The location of the 12 transmembrane domains is based on Olivier et al. (2001) and Rajogopalan et al. (2006). Transmembrane domain 2 in blue contains the sulfate motif defining the family. The properties of the amino acid side chains are indicated by different colors: polar (white), non-polar (blue), acidic (red), basic (green), and cysteine residues (yellow). Mutations utilized to generate knockin mouse models with modified prestin function (Dallos et al., 2008; Gao et al., 2007) are indicated with black arrows. Note that in the model by Gao et al (2007) residues K233, K235 and R236 are intracellular. Positive-selected amino acids in mammals detected by the evolutionary analysis performed by Franchini and Elgoyhen (2006) are highlighted with red circles and indicated with red arrows. Positive selected amino acids in echolocating bats detected by Li et al. (2008) are highlighted by violet circles and indicated with violet arrows. Positive selected amino acids in bats that co-evolved in dolphins display an additional green circle.

Figure 2

(A) Schematic representation of the structure of the α9α10 nicotinic receptor, showing the arrangement of the subunits according to the predicted stoichiometry determined by Plazas et al. (2005). (B) Amino acid sequence and secondary structure of the human α10 receptor (the topology of the predicted α-helical structure of transmembrane regions are not reproduced). The properties of the amino acid side chains are indicated by different colors: polar (white), non-polar (blue), acidic (red), basic (green), and cysteine residues (yellow). Loops A, B, C, and D highlighted in pink correspond to regions involved in agonist binding. The Cys-loop (blue) and the β1–β2 and β8–β9 (green) correspond to regions involved in gating of the channel. Positive selected amino acids in mammals detected by the evolutionary analysis performed by Franchini and Elgoyhen (2006) are highlighted with red circles and indicated with red arrows.