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Prestin is the motor protein of cochlear outer hair cells

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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Figure 1: Pres fragment identification.
Figure 2: Amino-acid sequence of gerbil prestin and its homology to rat pendrin.
Figure 3: Comparison of sulphate transport motifs.
Figure 4: Analysis of Pres expression in SMART cDNA from different tissues and at different developmental ages.
Figure 5: Voltage-dependent charge movement in TSA201 cells.
Figure 6: Examples of voltage-dependent motility expressed in TSA201 cells.

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References

  1. Dallos, P. in The Cochlea (eds Dallos, P., Popper, A. N. & Fay, R. R.) 1 –43 (Springer, New York, 1996).

    Google Scholar 

  2. Brownell, W. E., Bader, C. R., Bertrand, D. & de Ribaupierre, Y. Evoked mechanical responses of isolated outer hair cells. Science 227, 194–196 ( 1985).

    Article  ADS  CAS  Google Scholar 

  3. 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).

    Article  CAS  Google Scholar 

  4. Santos-Sacchi, J. & Dilger, J. P. Whole cell currents and mechanical responses of isolated outer hair cells. Hearing Res. 35, 143–150 ( 1988).

    Article  CAS  Google Scholar 

  5. Kachar, B., Brownell, W. E., Altschuler, R. A. & Fex, J. Electrokinetic shape changes of cochlear outer hair cells. Nature 322, 365–368 ( 1986).

    Article  ADS  CAS  Google Scholar 

  6. 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).

    Article  ADS  CAS  Google Scholar 

  7. Dallos, P. & Evans, B. N. High frequency motility of outer hair cells and the cochlear amplifier. Science 267, 2006–2009 (1995).

    Article  ADS  CAS  Google Scholar 

  8. 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).

    Article  ADS  CAS  Google Scholar 

  9. Ashmore, J. F. in Mechanics of Hearing (eds Kemp, D. & Wilson, J. P.) 107– 113 (Plenum, New York, 1999).

    Google Scholar 

  10. Santos-Sacchi, J. Reversible inhibition of voltage-dependent outer hair cell motility and capacitance. J. Neurosci. 11, 3096– 3110 (1991).

    Article  CAS  Google Scholar 

  11. 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).

    Article  CAS  Google Scholar 

  12. Ashmore, J. F. in Sensory Transduction (eds Corey, D. P. & Roper, S. D.) 395–412 (Rockefeller Univ. Press, New York, 1992).

    Google Scholar 

  13. 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).

    Article  ADS  Google Scholar 

  14. Dallos, P., Evans, B. N. & Hallworth, R. On the nature of the motor element in cochlear outer hair cells. Nature 350, 155– 157 (1991).

    Article  ADS  CAS  Google Scholar 

  15. 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).

    Article  CAS  Google Scholar 

  16. Forge, A. Structural features of the lateral walls in mammalian cochlear outer hair cells. Cell Tissue Res. 265, 473– 483 (1991).

    Article  CAS  Google Scholar 

  17. Kalinec, F. & Kachar, B. Inhibition of outer hair cell electromotility by sulfhydryl specific reagents. Neurosci. Lett. 157 , 231–234 (1993).

    Article  CAS  Google Scholar 

  18. Knipper, M. et al. Immunological identification of candidate proteins involved in regulating shape changes of outer hair cells. Hearing Res. 86, 100–1100 (1995).

    Article  CAS  Google Scholar 

  19. 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).

    Article  Google Scholar 

  20. 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).

    Article  CAS  Google Scholar 

  21. 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).

    Article  ADS  Google Scholar 

  22. Kozak, M. An analysis of 5′ noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 15, 8125– 8148 (1987).

    Article  CAS  Google Scholar 

  23. Everett, L. A. et al. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nature Genet. 17, 411–422 (1997).

    Article  CAS  Google Scholar 

  24. 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).

    Google Scholar 

  25. 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).

    Article  Google Scholar 

  26. 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).

    Article  CAS  Google Scholar 

  27. 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).

  28. Hofman, K. & Stoffel, W. Tmbase—a database of membrane spanning protein segments. Biol. Chem. 374, 166 (1993).

    Google Scholar 

  29. 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).

    Article  CAS  Google Scholar 

  30. Holley, M. C., Kalinec, F. & Kachar, B. Structure of the cortical cytoskeleton in mammalian outer hair cells. J. Cell. Sci. 102, 569 –580 (1992).

    PubMed  Google Scholar 

  31. Souter, M., Nevill, G. & Forge, A. Postnatal development of membrane specialisations of gerbil outer hair cells. Hearing Res. 91, 43– 62 (1995).

    Article  CAS  Google Scholar 

  32. Iwasa, K. H. Effect of stress on the membrane capacitance of the auditory outer hair cell. Biophys. J. 65, 492–498 (1993).

    Article  ADS  CAS  Google Scholar 

  33. 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).

    Article  CAS  Google Scholar 

  34. 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).

    Article  CAS  Google Scholar 

  35. 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).

    Article  CAS  Google Scholar 

  36. 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).

    Article  ADS  CAS  Google Scholar 

  37. 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).

    Article  ADS  CAS  Google Scholar 

  38. 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).

    Article  ADS  CAS  Google Scholar 

  39. Evans, B. N., Dallos, P. & Hallworth, R. in Cochlear Mechanisms (eds Wilson, J. P. & Kemp, D. T.) 205–206 (Plenum, London, 1989).

    Google Scholar 

  40. 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).

    Article  CAS  Google Scholar 

  41. 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).

    Article  Google Scholar 

  42. Hudspeth, A. J. Mechanical amplification of stimuli by hair cells. Curr. Opin. Neurobiol. 7, 480–486 ( 1997).

    Article  CAS  Google Scholar 

  43. Iwasa, K. H. & Adachi, M. Force generation in the outer hair cell of the cochlea. Biophys. J. 73, 546 –555 (1997).

    Article  ADS  CAS  Google Scholar 

  44. Svoboda, K. & Block, S. M. Force and velocity measured for single kinesin molecules. Cell 77, 773– 784 (1994).

    Article  CAS  Google Scholar 

  45. 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).

    Article  Google Scholar 

  46. Margolskee, R. F., McHendry-Rinde, B. & Horn, R. Panning transfected cells for electrophysiological studies. Biotechniques 15, 906– 911 (1993).

    CAS  PubMed  Google Scholar 

  47. Graham, F. L. & van der Eb, A. J. Transformation of rat cells by DNA of human adenovirus 5. Virology 54, 536–539 (1973).

    Article  CAS  Google Scholar 

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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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Correspondence to Peter Dallos.

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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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