Dissecting the electromechanical coupling mechanism of the motorprotein prestin

Abstract

Prestin, which is a member of the solute carrier 26 anion transporter family (SLC26A5), is a voltage-dependent membrane-based motor protein that confers electromotility on mammalian cochlear outer hair cells (OHCs).1 OHCs are a mammalian innovation, their presence2 and their endowment with functional prestin is essential for normal hearing of mammals.3 In order to clarify the molecular mechanism underlying the voltage-dependent motility of prestin, precise description of the relation between voltage-induced prestin-associated charge movement and the resulting cell displacement is essential. By simultaneously measuring voltage-dependent charge movement, which is manifested in the nonlinear capacitance (NLC) of the cell membrane, and voltage-induced OHC displacement, we provided compelling experimental evidence that prestin-associated charge movement and the resulting electromotility are fully coupled, and that prestin has at least two voltage-dependent conformational transition steps. These findings provide a basis for understanding the molecular mechanism of prestin. Here we discuss the relevance of our finding in the elucidation of the voltage-dependent motor mechanism of prestin, and speculate about possible voltage sensing mechanisms of the molecule.