Interaction of prestin (SLC26A5) with monovalent intracellular anions.

Abstract

Outer hair cells (OHCs) of the mammalian cochlea are equipped with a specific form of cellular motility that is driven by changes of the membrane potential. This electromotility is a membrane-based process generated by the membrane protein prestin (SLC26A5). Current models suggest that prestin undergoes a force-generating conformational transition upon changes of the membrane potential. The voltage dependence of prestin needs to be mediated by a charged particle within the protein, a 'voltage sensor', that can move through the membrane electrical field to trigger these conformational rearrangements. Indeed, voltage sensor translocation can be measured as electrical charge transfer. Here, we review and extend data indicating that charge movement by prestin and consequently electromotility depend on the presence of small monovalent anions such as chloride and bicarbonate at the cytoplasmic side of the membrane. The voltage dependence of prestin varies with concentration and species of the anion present, consistent with a partial translocation of the anion through the membrane. Thus anions may act as extrinsic voltage sensors. These conclusions suggest that charge movement and subsequent conformational rearrangements may relate to anion transport by other SLC26 members. Insights into molecular properties of prestin may provide clues to common mechanisms of anion transport by SLC26 proteins.