SLC26A5
Description
The SLC26A5 (solute carrier family 26 member 5) is a protein-coding gene located on chromosome 7.
Prestin is a protein critical to sensitive hearing in mammals. It is encoded by the SLC26A5 (solute carrier anion transporter family 26, member 5) gene. Prestin is the motor protein of the outer hair cells of the inner ear of the mammalian cochlea. It is highly expressed in the outer hair cells and is not expressed in the nonmotile inner hair cells. Immunolocalization shows prestin is expressed in the lateral plasma membrane of the outer hair cells, the region where electromotility occurs. The expression pattern correlates with the appearance of outer hair cell electromotility.
== Function == Prestin is essential in auditory processing. It is specifically expressed in the lateral membrane of outer hair cells (OHCs) of the cochlea. There is no significant difference between prestin density in high-frequency and low-frequency regions of the cochlea in fully developed mammals. There is good evidence that prestin has undergone adaptive evolution in mammals associated with acquisition of high frequency hearing in mammals.
SLC26A5 is a voltage-sensitive motor protein that drives outer hair cell (OHC) electromotility (eM) and participates in sound amplification in the hearing organ. It converts changes in the transmembrane electric potential into mechanical displacements, coupling its expansion to the movement of a charged voltage sensor across the lipid membrane. The nature of the voltage sensor is not fully understood, with two competing models. The first model proposes that SLC26A5 acts as an incomplete transporter, where intracellular chloride anion acts as an extrinsic voltage sensor, driving conformational changes in the protein that produce a length change in the plane of the membrane and hence in the length of the OHC. The second model suggests multiple charged amino acid residues distributed at the intracellular and extracellular membrane interfaces form an intrinsic voltage sensor, whose movement produces the non-linear capacitance (NLC). However, the effective voltage sensor may be a hybrid, assembled from intrinsic charge (charged residues) and extrinsic charge (bound anion). Notably, anion binding to the anion-binding pocket partially neutralizes the intrinsic positive charge, and the remaining charge may serve as a voltage sensor that, after depolarization, moves from a down (expanded state) to an up (contracted) conformation. This movement is accompanied by an eccentric contraction of the intermembrane cross-sectional area of the protein and a major increase in the hydrophobic thickness of the protein, resulting in plasma membrane thickening and cell contraction after membrane depolarization. The anion-binding pocket transitions from an inward-open (Down) state, exposed toward the intracellular solvent in the absence of anion, to the occluded (Up) state upon anion binding. Salicylate competes for the anion-binding site, inhibiting the voltage-sensor movement and, therefore, the charge transfer and electromotility by displacing Cl(-) from the anion-binding site and preventing the structural transitions to the contracted state. Additionally, SLC26A5 can act as a weak Cl(-)/HCO3(-) antiporter across the cell membrane, regulating the intracellular pH of the OHCs, although it was initially found to be unable to mediate electrogenic anion transport. Furthermore, SLC26A5 supports a role in cardiac mechanical amplification, serving as an elastic element to enhance the actomyosin-based sarcomere contraction system.
SLC26A5 is also known as DFNB61, PRES.
