Key Points
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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).
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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.
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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.
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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.
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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.
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The functional properties of prestin strongly support the concept of a single protein acting as an electromechanical transducer in OHCs.
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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.
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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.
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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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References
Hudspeth, A. J. Mechanical amplification of stimuli by hair cells. Curr. Opin. Neurobiol. 7, 480–486 (1997).
Brownell, W. E., Bader, C. R., Bertrand, D. & De Ribaupierre, Y. Evoked mechanical responses of isolated cochlear hair cells. Science 227, 194–196 (1985).The first demonstration of OHC electromotility.
Zheng, J. et al. Prestin is the motor protein of cochlear outer hair cells. Nature 405, 149–155 (2000).The first description of cloning, tissue specificity and developmental pattern of Prestin , which showed that prestin confers motility and nonlinear capacitance on a heterologous system.
Flock, Å., Kimura, R., Lindquist, P. G. & Wersäll, J. Morphological basis of directional sensitivity of outer hair cells in the organ of Corti. J. Acoust. Soc. Am. 34, 1351–1355 (1962).
Hudspeth, A. J. & Corey, D. P. Sensitivity, polarity and conductance change in the response of vertebrate hair cells to controlled mechanical stimuli. Proc. Natl Acad. Sci. USA 74, 2407–2411 (1977).
Evans, B. N. & Dallos, P. Stereocilia displacement induced somatic motility of cochlear outer hair cells. Proc. Natl Acad. Sci. USA 90, 8347–8351 (1993).
Iwasa, K. Effect of stress on the membrane capacitance of the auditory outer hair cell. Biophys. J. 65, 492–498 (1993).
Ashmore, J. F. A fast motile response in guinea pig outer hair cells: the basis of the cochlear amplifier. J. Physiol. (Lond.) 388, 323–347 (1987).A systematic study of electromotility in OHCs.
Ryan, A. & Dallos, P. Absence of cochlear outer hair cells: effect on behavioural auditory threshold. Nature 253, 44–46 (1975).
Dallos, P. & Harris, D. Properties of auditory nerve responses in the absence of outer hair cells. J. Neurophysiol. 41, 365–383 (1978).
Holley, M. C. in The Cochlea (eds Dallos, P., Popper, A. & Fay, R.) 386–434 (Springer, New York, 1996).
Kachar, B., Brownell, W. E., Altschuler, R. & Fex, J. Electrokinetic shape changes of cochlear outer hair cells. Nature 322, 365–368 (1986).
Holley, M. C. & Ashmore, J. F. On the mechanism of a high-frequency force generator in outer hair cells isolated from the guinea pig cochlea. Proc. R. Soc. Lond. B 232, 413–429 (1988).
Dallos, P. & Evans, B. N. High frequency motility of outer hair cells and the cochlear amplifier. Science 267, 2006–2009 (1995).
Frank, G., Hemmert, W. & Gummer, A. W. Limiting dynamics of high-frequency electromechanical transduction of outer hair cells. Proc. Natl Acad. Sci. USA 96, 4420–4425 (1999).
Mountain, D. C. & Hubbard, A. L. A piezoelectric model for outer hair cell function. J. Acoust. Soc. Am. 95, 350–354 (1994).
Dallos, P., Hallworth, R. & Evans, B. N. Theory of electrically-driven shape changes of cochlear outer hair cells. J. Neurophysiol. 70, 299–323 (1993).
Armstrong, C. M. & Bezanilla, F. Inactivation of the sodium channel. II. Gating current experiments. J. Gen. Physiol. 70, 567–590 (1977).
Stühmer, W. et al. Structural parts involved in activation and inactivation of the sodium channel. Nature 339, 597–603 (1989).
Forge, A., Davies, S. & Zajic, G. Assessment of ultrastructure in isolated cochlear hair cells using a procedure for rapid freezing before freeze-fracture and deep-etching. J. Neurocytol. 20, 471–484 (1991).
Ashmore, J. F. Forward and reverse transduction in the mammalian cochlea. Neurosci Res Suppl 12, S39–S50 (1990).The first demonstration that gating current accompanies electromotility in OHCs.
Santos-Sacchi, J. Reversible inhibition of voltage-dependent outer hair cell motility and capacitance. J. Neurosci. 11, 3096–3110 (1991).
Weiss, T. F. Bidirectional transduction in vertebrate hair cells: a mechanism for coupling mechanical and electrical processes. Hear. Res. 7, 353–360 (1982).
Gale, J. E. & Ashmore, J. F. Charge displacement induced by rapid stretch in the basolateral membrane of the guinea-pig outer hair cell. Proc. R. Soc. Lond. B 255, 243–249 (1994).
Kakehata, S. & Santos-Sacchi, J. Membrane tension directly shifts voltage dependence of outer hair cell motility and associated gating charge. Biophys. J. 68, 2190–2197 (1995).
Oghalai, J. S., Zhao, H.-B., Kutz, J. W. & Brownell, W. E. Voltage- and tension-dependent lipid mobility in the outer hair cell plasma membrane. Science 287, 658–661 (2000).
Lim, D. J. & Kalinec, F. Cell and molecular basis of hearing. Kidney Int Suppl 65, S104–S113 (1998).
Ludwig, J. et al. Reciprocal electromechanical properties of rat prestin: the motor molecule from rat outer hair cells. Proc. Natl Acad. Sci. USA 98, 4178–4183 (2001).An extensive investigation of the reciprocal behaviour of prestin and its membrane topology.
Oliver, D. et al. Intracellular anions as the voltage-sensor of prestin, the outer hair cell motor protein. Science 292, 2340–2343 (2001).The demonstration that prestin functions with an extrinsic voltage sensor, comprised of intracellular anions that are bound to the protein.
Santos-Sacchi, J., Shen, W., Zheng, J. & Dallos, P. Effects of membrane potential and tension on prestin, the outer hair cell membrane protein. J. Physiol. (Lond.) 531, 661–666 (2001).
Belyantseva, I. A., Adler, H. J., Curi, R., Frolenkov, G. I. & Kachar, B. Expression and localization of prestin and the sugar transporter GLUT-5 during development of electromotility of cochlear outer hair cells. J. Neurosci. 20, RC116 (1–5) (2000).
Zheng, J., Long, K. B., Shen, W., Madison, L. D. & Dallos, P. Prestin topology: localization of protein epitopes in relation to the plasma membrane. NeuroReport 12, 1929–1935 (2001).
He, D. Z., Evans, B. N. & Dallos, P. First appearance and development of electromotility in neonatal gerbil outer hair cells. Hear. Res. 78, 77–90 (1994).
Oliver, D. & Fakler, B. Expression density and functional characteristics of the outer hair cell motor protein are regulated during postnatal development in rat. J. Physiol. (Lond.) 519, 791–800 (1999).
Soleimani, M. et al. Pendrin: an apical Cl−/OH−/HCO3− exchanger in the kidney cortex. Am J Physiol Renal Physiol 280, F356–F364 (2001).
Wang, Z., Petrovic, S., Mann, E. & Soleimani, M. Identification of an apical Cl−/HCO3− exchanger in the small intestine. Am. J. Physiol. (in the press).
Gale, J. E. & Ashmore, J. F. An intrinsic frequency limit to the cochlear amplifier. Nature 389, 63–66 (1997).
Fahlke, C. Ion permeation and selectivity in ClC-type chloride channels. Am J Physiol Renal Physiol 280, F748–F757 (2001).
Tunstall, M. J., Gale, J. E. & Ashmore, J. F. Action of salicylate on membrane capacitance of outer hair cells from the guinea-pig cochlea. J. Physiol. 485, 739–752 (1995).
Kakehata, S. & Santos-Sacchi, J. Effects of salicylate and lanthanides on outer hair cell motility and associated gating charge. J. Neurosci. 16, 4881–4889 (1996).
Shehata, W. E., Brownell, W. E. & Dieler, R. Effects of salicylate on shape, electromotility, and membrane characteristics of isolated outer hair cells from the guinea pig cochlea. Acta Otolaryngol 111, 707–718 (1991).
Zhang, P.-C., Keleshian, A. M. & Sachs, F. Voltage-induced membrane movement. Nature 413, 428–432 (2001).
Raphael, R. M., Popel, A. S. & Brownell, W. E. A membrane bending model of outer hair cell electromotility. Biophys. J. 78, 2844–2862 (2000).
Wu, M. & Santos-Sacchi, J. Effects of lipophilic ions on outer hair cell membrane capacitance and motility. J. Membr. Biol. 166, 111–118 (1998).
Dallos, P. The active cochlea. J. Neurosci. 12, 4575–4585 (1992).A review of amplification in the cochlea by OHCs.
Nobili, R., Mammano, F. & Ashmore, J. How well do we understand the cochlea? Trends Neurosci. 21, 159–167 (1998).
Markin, V. S. & Hudspeth, A. J. Gating spring models of mechanoelectrical transduction by hair cells of the internal ear. Annu. Rev. Biophys. Biomol. Struct. 24, 59–83 (1995).
Eatock, R. A. Adaptation in hair cells. Annu. Rev. Neurosci. 23, 285–314 (2000).
Dallos, P. Response characteristics of mammalian cochlear hair cells. J. Neurosci. 5, 1591–1608 (1985).
Lohi, H. et al. Mapping of five new putative anion transporter genes in human and characterization of SLC26A6, a candidate gene for pancreatic anion exchanger. Genomics 70, 102–112 (2000).
Waldegger, S. et al. Cloning and characterization of SLC26A6, a novel member of the solute carrier 26 gene family. Genomics 72, 43–50 (2001).
Everett, L. A. et al. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nature Genet. 17, 411–422 (1997).
Knauf, F. et al. Identification of a chloride–formate exchanger expressed on the brush border membrane of renal proximal tubule cells. Proc. Natl Acad. Sci. USA (in the press).
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Glossary
- ACUSTICO-LATERALIS SYSTEMS
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All hair-cell based vertebrate sense organs: auditory, vestibular and lateral line.
- CAPACITANCE
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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
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(NLC). The voltage-dependent capacitance that arises from the movement of charge that is driven by changes in the transmembrane potential.
- PIEZO-ELEMENT
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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
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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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DOI: https://doi.org/10.1038/nrm730
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