Abstract
The outer and inner hair cells of the mammalian cochlea perform different functions. In response to changes in membrane potential, the cylindrical outer hair cell rapidly alters its length and stiffness. These mechanical changes, driven by putative molecular motors, are assumed to produce amplification of vibrations in the cochlea that are transduced by inner hair cells. Here we have identified an abundant complementary DNA from a gene, designated Prestin, which is specifically expressed in outer hair cells. Regions of the encoded protein show moderate sequence similarity to pendrin and related sulphate/anion transport proteins. Voltage-induced shape changes can be elicited in cultured human kidney cells that express prestin. The mechanical response of outer hair cells to voltage change is accompanied by a ‘gating current’, which is manifested as nonlinear capacitance. We also demonstrate this nonlinear capacitance in transfected kidney cells. We conclude that prestin is the motor protein of the cochlear outer hair cell.
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References
Dallos, P. in The Cochlea (eds Dallos, P., Popper, A. N. & Fay, R. R.) 1 –43 (Springer, New York, 1996).
Brownell, W. E., Bader, C. R., Bertrand, D. & de Ribaupierre, Y. Evoked mechanical responses of isolated outer hair cells. Science 227, 194–196 ( 1985).
Ashmore, J. F. A fast motile response in guinea-pig outer hair cells: the cellular basis of the cochlear amplifier. J. Physiol. (Lond.) 388, 323–347 (1987).
Santos-Sacchi, J. & Dilger, J. P. Whole cell currents and mechanical responses of isolated outer hair cells. Hearing Res. 35, 143–150 ( 1988).
Kachar, B., Brownell, W. E., Altschuler, R. A. & Fex, J. Electrokinetic shape changes of cochlear outer hair cells. Nature 322, 365–368 ( 1986).
Holley, M. C. & Ashmore, J. F. On the mechanisms of a high frequency force generator in outer hair cells isolated from the guinea pig cochlea. Proc. R. Soc. Lond. Ser. 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).
Ashmore, J. F. in Mechanics of Hearing (eds Kemp, D. & Wilson, J. P.) 107– 113 (Plenum, New York, 1999).
Santos-Sacchi, J. Reversible inhibition of voltage-dependent outer hair cell motility and capacitance. J. Neurosci. 11, 3096– 3110 (1991).
Armstrong, C. M. & Bezanilla, F. Charge movement associated with the opening and closing of the activation gates of the Na channels. J. Gen. Physiol. 63, 533– 552 (1974).
Ashmore, J. F. in Sensory Transduction (eds Corey, D. P. & Roper, S. D.) 395–412 (Rockefeller Univ. Press, New York, 1992).
He, D. Z. Z. & Dallos, P. Somatic stiffness of cochlear outer hair cells is voltage dependent. Proc. Natl Acad. Sci. USA 96, 8223–8228 (1999).
Dallos, P., Evans, B. N. & Hallworth, R. On the nature of the motor element in cochlear outer hair cells. Nature 350, 155– 157 (1991).
Huang, G. & Santos-Sacchi, J. Mapping the distribution of the outer hair cell motility voltage sensor by electrical amputation. Biophys. J. 65, 2228–2236 (1993).
Forge, A. Structural features of the lateral walls in mammalian cochlear outer hair cells. Cell Tissue Res. 265, 473– 483 (1991).
Kalinec, F. & Kachar, B. Inhibition of outer hair cell electromotility by sulfhydryl specific reagents. Neurosci. Lett. 157 , 231–234 (1993).
Knipper, M. et al. Immunological identification of candidate proteins involved in regulating shape changes of outer hair cells. Hearing Res. 86, 100–1100 (1995).
Géléoc, G. S. G., Casalotti, S. O., Forge, A. & Ashmore, J. F. A sugar transporter as a candidate for the outer hair cell motor. Nature Neurosci. 2, 713 –719 (1999).
He, D. Z. Z., Evans, B. N. & Dallos, P. First appearance and development of electromotility in neonatal gerbil outer hair cells. Hearing Res. 78 , 77–90 (1994).
Diatchanko, L. et al. Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries. Proc. Natl Acad. Sci. USA 93, 6025– 6030 (1996).
Kozak, M. An analysis of 5′ noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 15, 8125– 8148 (1987).
Everett, L. A. et al. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nature Genet. 17, 411–422 (1997).
Moseley, R. H. et al. Downregulated in adenoma gene encodes a chloride transporter defective in congenital chloride diarrhea. Am. J. Physiol. 276, 185–192 (1999).
Scott, D. A., Wang, R., Kreman, T. M., Sheffield, V. C. & Karniski, L. P. The Pendred syndrome gene encodes a chloride–iodide transport protein. Nature Genet. 4, 440– 443 (1999).
Everett, L. A. & Green, E. D. A family of mammalian anion transporters and their involvement in human genetic diseases. Hum. Mol. Genet. 8, 1883–1891 (1999).
Sonnhammer, E. L. L., Heijne, G. von & Krogh, A. A hidden Markov model for predicting transmembrane helices in protein sequences. Proc. 6th Int. conf. Intelligent Syst. Mol. Biol. (ISMB98) (eds Glasgow, J. et al.) 175– 182 (Amer. Assoc. for Artificial Intelligence Press, Menlo Park, CA, 1998).
Hofman, K. & Stoffel, W. Tmbase—a database of membrane spanning protein segments. Biol. Chem. 374, 166 (1993).
Sandal, N. N. & Marcker, K. A. Similarities between a soybean nodulin, Neurospora crassa sulphate permease II and a putative human tumour suppressor. Trends Biochem. Sci. 19, 19 (1994).
Holley, M. C., Kalinec, F. & Kachar, B. Structure of the cortical cytoskeleton in mammalian outer hair cells. J. Cell. Sci. 102, 569 –580 (1992).
Souter, M., Nevill, G. & Forge, A. Postnatal development of membrane specialisations of gerbil outer hair cells. Hearing Res. 91, 43– 62 (1995).
Iwasa, K. H. Effect of stress on the membrane capacitance of the auditory outer hair cell. Biophys. J. 65, 492–498 (1993).
Shehata, W., Brownell, W. E. & Dieler, R. Effects of salicylate on shape, electromotility and membrane characteristics of isolated hair cells from the guinea pig cochlea. Acta Oto-Laryngol. (Stockholm) 111, 707 –718 (1991).
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).
Tunstall, M. J., Gale, L. E. & Ashmore, J. F. Action of salicylate on membrane capacitance of outer hair cells from the guinea-pig cochlea. J. Physiol. (London) 485, 739–752 (1995).
Kalinec, F., Holley, M. C., Iwasa, K., Lim, D. J. & Kachar, B. A membrane-based force generation mechanism in auditory sensory cells. Proc. Natl Acad. Sci. USA 89, 8671–8675 (1992).
Huang, G. J. & Santos-Sacchi, J. Motility voltage sensor of the outer hair cell resides within the lateral plasma membrane. Proc. Natl Acad. Sci. USA 91, 12268– 12272 (1994).
Adachi, M. & Iwasa, K. H. Electrically driven motor in the outer hair cell: effect of a mechanical constraint. Proc. Natl Acad. Sci. USA 96, 7244–7249 (1999).
Evans, B. N., Dallos, P. & Hallworth, R. in Cochlear Mechanisms (eds Wilson, J. P. & Kemp, D. T.) 205–206 (Plenum, London, 1989).
Mustapha, M. et al. Identification of a locus on chromosome 7q31, DFNB14, responsible for prelingual sensorineural non-syndromic deafness. Eur. J. Hum. Genet. 6, 548–551 ( 1998).
Greinwald, J. H. Jr et al. Localization of a novel gene for nonsyndromic hearing loss (DFNB17) to chromosome region 7q31. Am. J. Med. Genet. 78, 107–113 ( 1998).
Hudspeth, A. J. Mechanical amplification of stimuli by hair cells. Curr. Opin. Neurobiol. 7, 480–486 ( 1997).
Iwasa, K. H. & Adachi, M. Force generation in the outer hair cell of the cochlea. Biophys. J. 73, 546 –555 (1997).
Svoboda, K. & Block, S. M. Force and velocity measured for single kinesin molecules. Cell 77, 773– 784 (1994).
He, D. Z. Z. Relationship between the development of outer hair cell electromotility and efferent innervation: a study in cultured organ of Corti of neonatal gerbils. J. Neurosci. 15, 3634– 3643 (1997).
Margolskee, R. F., McHendry-Rinde, B. & Horn, R. Panning transfected cells for electrophysiological studies. Biotechniques 15, 906– 911 (1993).
Graham, F. L. & van der Eb, A. J. Transformation of rat cells by DNA of human adenovirus 5. Virology 54, 536–539 (1973).
Acknowledgements
We thank L. H. Pinto and J. S. Takahashi for their comments on the manuscript. We also thank P. Kopp for providing the human pendrin cDNA, B. Schulte for providing the λgt11 gerbil cochlea library, and Y. Tang, M. Brenner and J. Cheng for technical assistance. This work was primarily supported by a Senior Fellowship from the McKnight Endowment Fund for Neuroscience to P.D. and the National Institute on Deafness and other Communication Disorders, NIH.
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Zheng, J., Shen, W., He, D. et al. Prestin is the motor protein of cochlear outer hair cells. Nature 405, 149–155 (2000). https://doi.org/10.1038/35012009
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DOI: https://doi.org/10.1038/35012009
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