Prestin is a gene recently cloned from mammalian cochlear outer hair cells (OHC) using a single cell type, outer minus inner hair cell, specific suppressive subtractive hybridization procedure. The localization and gene expression profile of the prestin protein fits the pattern of OHC’s development of electromotility. When prestin is abundantly expressed in normally nonmotile kidney cells, nonlinear capacitance and motility that are normally only seen in OHCs can be recorded. Furthermore, both nonlinear capacitance and motility can be reduced by salicylate, a well-known inhibitor of electromotility. These data suggest that prestin is the motor protein of OHCs. Amino acid sequence and gene structure analysis indicate that prestin is the fifth member of a newly discovered anion transport family (SLC26) that includes PDS, DRA and DTDST, which are chloride-iodide transporters, Cl/HCO3 exchangers or sulfate transporters. Prestin shares overall structure similarity with this anion transporter family. Recently, intracellular anions (chloride or bicarbonate) were found to be essential for OHC electromotility and prestin’s function.

1.
Aravind L, Koonin EV: The STAS domain – a link between anion transporters and antisigma-factor antagonists. Curr Biol 2000;10:R53–R55.
2.
Ashmore JF: A fast motile response in guinea-pig outer hair cells: The cellular basis of the cochlear amplifier. J Physiol (Lond) 1987;388:323–347.
3.
Ashmore JF: Transducer motor coupling in cochlear outer hair cells; in Kemp D, Wilson JP (eds): Mechanics of Hearing. New York, Plenum, 1989, pp 107–113.
4.
Ashmore JF: Mammalian hearing and the cellular mechanisms of the cochlear amplifier. Soc Gen Physiol Ser 1992;47:395–412.
5.
Belyantseva IA, Adler HJ, Curi R, Frolenkov GI, Kachar B: Expression and localization of prestin and the sugar transporter GLUT-5 during development of electromotility in cochlear outer hair cells. J Neurosci 2000;20:RC116.
6.
Brownell WE, Bader CR, Bertrand D, de Ribaupierre Y: Evoked mechanical responses of isolated cochlear outer hair cells. Science 1985;227:194–196.
7.
Dallos P: The active cochlea. J Neurosci 1992;12:4575–4585.
8.
Dallos P, Evans BN: High-frequency motility of outer hair cells and the cochlear amplifier. Science 1995;267:2006–2009.
9.
Dallos P, Harris D: Properties of auditory nerve responses in absence of outer hair cells. J Neurophysiol 1978;41:365–383.
10.
Everett LA, Glaser B, Beck JC, Idol JR, Buchs A, Heyman M, Adawi F, Hazani E, Nassir E, Baxevanis AD, Sheffield VC, Green ED: Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet 1997;17:411–422.
11.
Forge A: Structural features of the lateral walls in mammalian cochlear outer hair cells. Cell Tissue Res 1991;265:473–483.
12.
Frank G, Hemmert W, Gummer AW: Limiting dynamics of high-frequency electromechanical transduction of outer hair cells. Proc Natl Acad Sci USA 1999;96:4420–4425.
13.
Géléoc GS, Casalotti SO, Forge A, Ashmore JF: A sugar transporter as a candidate for the outer hair cell motor. Nat Neurosci 1999;2:713–719.
14.
Hastbacka J, de la Chapelle A, Mahtani MM, Clines G, Reeve-Daly MP, Daly M, Hamilton BA, Kusumi K, Trivedi B, Weaver A, et al: The diastrophic dysplasia gene encodes a novel sulfate transporter: Positional cloning by fine-structure linkage disequilibrium mapping. Cell 1994;78:1073–1087.
15.
Hastbacka J, Superti-Furga A, Wilcox WR, Rimoin DL, Cohn DH, Lander ES: Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): Evidence for a phenotypic series involving three chondrodysplasias. Am J Hum Genet 1996;58:255–262.
16.
Holley MC: Outer hair cell motility; in Dallos P, Popper AN, Fay RR (eds): The Cochlea: Springer Handbook of Auditory Research. New York, Springer, 1996, pp 386–434.
17.
Holley MC, Ashmore JF: On the mechanism of a high-frequency force generator in outer hair cells isolated from the guinea pig cochlea. Proc R Soc Lond B Biol Sci 1988;232:413–429.
18.
Huang G, Santos-Sacchi J: Mapping the distribution of the outer hair cell motility voltage sensor by electrical amputation. Biophys J 1993;65:2228–2236.
19.
Hudspeth AJ: How the ear’s works work. Nature 1989;341:397–404.
20.
Kachar B, Brownell WE, Altschuler R, Fex J: Electrokinetic shape changes of cochlear outer hair cells. Nature 1986;322:365–368.
21.
Kakehata S, Santos-Sacchi J: Effects of salicylate and lanthanides on outer hair cell motility and associated gating charge. J Neurosci 1996;16:4881–4889.
22.
Kalinec F, Holley MC, Iwasa KH, Lim DJ, Kachar B: A membrane-based force generation mechanism in auditory sensory cells. Proc Natl Acad Sci USA 1992;89:8671–8675.
23.
Kalinec F, Kachar B: Inhibition of outer hair cell electromotility by sulfhydryl specific reagents. Neurosci Lett 1993;157:231–234.
24.
Kere J, Lohi H, Hoglund P: Genetic disorders of membrane transport. III. Congenital chloride diarrhea. Am J Physiol 1999;276:G7–G13.
25.
Knipper M, Zimmermann U, Kopschall I, Rohbock K, Jungling S, Zenner HP: Immunological identification of candidate proteins involved in regulating active shape changes of outer hair cells. Hear Res 1995;86:100–110.
26.
Lohi H, Kujala M, Kerkela E, Saarialho-Kere U, Kestila M, Kere J: Mapping of five new putative anion transporter genes in human and characterization of SLC26A6, a candidate gene for pancreatic anion exchanger. Genomics 2000;70:102–112.
27.
Ludwig J, Oliver D, Frank G, Klocker N, Gummer AW, Fakler B: Reciprocal electromechanical properties of rat prestin: The motor molecule from rat outer hair cells. Proc Natl Acad Sci USA 2001;98:4178–4183.
28.
Oliver D, He DZ, Klocker N, Ludwig J, Schulte U, Waldegger S, Ruppersberg JP, Dallos P, Fakler B: Intracellular anions as the voltage-sensor of prestin, the outer hair cell motor protein. Science 2001;292:2340–2343.
29.
Ryan A, Dallos P: Effect of absence of cochlear outer hair cells on behavioural auditory threshold. Nature 1975;253:44–46.
30.
Santos-Sacchi J: Asymmetry in voltage-dependent movements of isolated outer hair cells from the organ of Corti. J Neurosci 1989;9:2954–2962.
31.
Santos-Sacchi J: Reversible inhibition of voltage-dependent outer hair cell motility and capacitance. J Neurosci 1991;11:3096–3110.
32.
Santos-Sacchi J, Dilger JP: Whole cell currents and mechanical responses of isolated outer hair cells. Hear Res 1988;35:143–150.
33.
Santos-Sacchi J, Shen W, Zheng J, Dallos P: Effects of membrane potential and tension on prestin, the outer hair cell lateral membrane motor protein. J Physiol 2001;531:661–666.
34.
Scott DA, Wang R, Kreman TM, Sheffield VC, Karniski LP: The Pendred syndrome gene encodes a chloride-iodide transport protein. Nat Genet 1999;21:440–443.
35.
Shehata WE, Brownell WE, Dieler R: Effects of salicylate on shape, electromotility and membrane characteristics of isolated outer hair cells from guinea pig cochlea. Acta Otolaryngol 1991;111:707–718.
36.
Soleimani M, Greeley T, Petrovic S, Wang Z, Amlal H, Kopp P, Burnham CE: Pendrin: An apical Cl/OH/HCO3 exchanger in the kidney cortex. Am J Physiol Renal Physiol 2001;280:F356–364.
37.
Superti-Furga A, Hastbacka J, Wilcox WR, Cohn DH, van der Harten HJ, Rossi A, Blau N, Rimoin DL, Steinmann B, Lander ES, Gitzelmann R: Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene. Nat Genet 1996;12:100–102.
38.
Tunstall MJ, Gale JE, Ashmore JF: Action of salicylate on membrane capacitance of outer hair cells from the guinea-pig cochlea. J Physiol (Lond) 1995;485:739–752.
39.
Zheng J, Long KB, Shen W, Madison LD, Dallos P: Prestin topology: Localization of protein epitopes in relation to the plasma membrane. Neuroreport 2001;12:1929–1935.
40.
Zheng J, Shen W, He DZ, Long KB, Madison LD, Dallos P: Prestin is the motor protein of cochlear outer hair cells. Nature 2000;405:149–155.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.