Prestin (SLC26A5), a member of the SLC26 anion transporter family, is the motor molecule of mammalian outer hair cells (OHCs). As a result of Prestin's motor activity, OHCs respond to membrane voltage changes with macroscopic length changes, termed electromotility. Electromotility is believed to contribute to enhancement of hearing sensitivity and frequency selectivity. Prestin´s electromotile properties result from voltage-dependent movements of a charged voltage sensor, subsequently triggering a force-producing conformational reorientation of the protein. Movement of the voltage sensor through the membrane's electrical field gives rise to a voltage-dependent membrane capacitance (non-linear capacitance, NLC). We previously suggested that electromotility may be related to a partial anion transport cycle. To investigate this hypothesis, we cloned Prestin orthologs from chicken and zebrafish. These non-mammalian SLC26A5 proteins are electrogenic divalent/Cl exchangers with a

1:1 stoichiometry. However, they do not generate electromotility. By contrast, Prestin is not a functional anion transporter, but generates electromotility. Mutational exchange of small sequence stretches conferred motility-related NLC to non-mammalian SLC26A5 anion transporters. Equivalently, transferring circumscribed parts of zebrafish SLC26A5 onto the mammalian ortholog enabled functional anion transport. Thus, minor changes in amino acid sequence can convert an anion exchanger into a voltage-driven membrane motor and vice versa.