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  • Review Article
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Prestin, a new type of motor protein

Key Points

  • The mammalian ear relies on a mechanical amplification process to achieve its remarkable sensitivity and frequency selectivity. Amplification depends on one of two types of sensory receptor cell in the cochlea, called the outer hair cells (OHC).

  • Two candidate mechanisms have been considered for amplification. Like their operation in non-mammalian vertebrates, feedback could be supplied by the mechanotransducer channels that are located in the stereocilia. Alternatively, the electromotility of OHCs, comprising voltage-dependent length changes of the cells, could be the amplifier process.

  • It is assumed that OHC electromotility is driven by specialized motor molecules that are located in the cell membrane. Recently, on the basis of subtractive cloning between motile OHCs and non-motile inner hair cells, a cDNA that is specifically expressed in OHCs was isolated and termed Prestin.

  • Prestin is a member of the newly emerging gene family that codes for anion-transporter-related proteins, called solute carrier family (SLC)26. The protein prestin, however, does not seem to transport anions; it is a polypeptide of 744 residues with a molecular weight of 80 kDa.

  • When heterologously expressed in mammalian cell lines, prestin shows all the hallmarks of the OHC motor protein — it endows transfected cells with nonlinear capacitance and the prestin-expressing cells are electromotile. Prestin gene and protein expression perfectly parallels the developmental time course that was previously determined for the electromotility of OHCs.

  • The functional properties of prestin strongly support the concept of a single protein acting as an electromechanical transducer in OHCs.

  • Prestin is a new type of biological motor. It is entirely different from the well-known and much-studied classical cellular motors in that its function is not based on enzymatic processes, but on direct voltage-to-displacement conversion. The action of prestin is also orders of magnitude faster than that of any other cellular motor protein, as it functions at microsecond rates.

  • On the basis of functional analysis of mutant forms of prestin, it has been shown that the protein uses an extrinsic voltage sensor: monovalent anions that are available in the cytoplasm. Available anions, principally Cl, bind to a site and are translocated across the membrane in response to changes in the transmembrane voltage. This translocation triggers conformational changes in the protein, and results in a change of cell-surface area and, consequently, a change in cell length.

  • It seems as if prestin acts as an incomplete transporter. It swings anions across the cell membrane, but does not allow them to dissociate and escape to the extracellular space.

Abstract

Prestin, a transmembrane protein found in the outer hair cells of the cochlea, represents a new type of molecular motor, which is likely to be of great interest to molecular cell biologists. In contrast to enzymatic-activity-based motors, prestin is a direct voltage-to-force converter, which uses cytoplasmic anions as extrinsic voltage sensors and can operate at microsecond rates. As prestin mediates changes in outer hair cell length in response to membrane potential variations, it might be responsible for sound amplification in the mammalian hearing organ.

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Figure 1: Amplification in the cochlea by outer hair cells.
Figure 2: Cartoon of the membrane topology of prestin.
Figure 3: Model of the control of prestin by internal Cl ions.

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Authors and Affiliations

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Correspondence to Peter Dallos.

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DATABASES

Entrez

AF230376

AJ303372

AY024359

 Interpro

STAS domain

 OMIM

achondrogenesis type IB

chloride diarrhoea

DFNB4

Pendred syndrome

 Swiss-Prot

prestin

SLC26A1

SLC26A2

SLC26A3

SLC26A4

SLC26A6

Glossary

ACUSTICO-LATERALIS SYSTEMS

All hair-cell based vertebrate sense organs: auditory, vestibular and lateral line.

CAPACITANCE

The property of an electric nonconductor (dielectric) to separate charges to the two opposite surfaces of the dielectric when these surfaces are maintained at different voltages.

NONLINEAR CAPACITANCE

(NLC). The voltage-dependent capacitance that arises from the movement of charge that is driven by changes in the transmembrane potential.

PIEZO-ELEMENT

A ceramic that changes its length (mechanical energy) when stimulated electrically, and produces electrical energy (voltage) when mechanical force acts on it.

PASSIVE ELECTRICAL CAPACITANCE

The voltage-independent capacitance that arises from the fact that cell membranes act as a condenser (a device that has electrical capacitance) with the lipids constituting the dielectric (an electrical insulator).

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Dallos, P., Fakler, B. Prestin, a new type of motor protein. Nat Rev Mol Cell Biol 3, 104–111 (2002). https://doi.org/10.1038/nrm730

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