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Mechanotransduction and Inner Ear Function

  • Wei XiongEmail author
Chapter
Part of the SpringerBriefs in Biochemistry and Molecular Biology book series (BRIEFSBIOCHEM)

Abstract

Hair-cell mechanotransduction (MET) plays so important a role in auditory sensation that its malfunction introduces severe hearing impairment. In this chapter, we listed all of the known genes linked to MET functionality, which was collectively learned from studies on mouse models and human genetics. It might give us implication in how the hearing disorder happens due to MET defect. Based on this knowledge, we would like to discuss some physiological significance of MET and potential therapeutics to treat hearing loss.

Keywords

Human genetics Mouse models Cochlear tuning Inner ear dysfunction Gene therapy 

References

  1. 1.
    Michel, V., et al. 2017. CIB2, defective in isolated deafness, is key for auditory hair cell mechanotransduction and survival. EMBO Molecular Medicine 9: 1711–1731.CrossRefGoogle Scholar
  2. 2.
    Riazuddin, S., et al. 2012. Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48. Nature Genetics 44 (11): 1265–1271.CrossRefGoogle Scholar
  3. 3.
    Booth, K.T., et al. 2017. Variants in CIB2 cause DFNB48 and not USH1J. Clinical Genetics.  https://doi.org/10.1111/cge.13170.
  4. 4.
    Bitner-Glindzicz, M., et al. 2000. A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene. Nature Genetics 26 (1): 56–60.CrossRefGoogle Scholar
  5. 5.
    Verpy, E., et al. 2000. A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C. Nature Genetics 26 (1): 51–55.CrossRefGoogle Scholar
  6. 6.
    Siemens, J., et al. 2002. The Usher syndrome proteins cadherin 23 and harmonin form a complex by means of PDZ-domain interactions. Proceedings of the National Academy of Sciences of the United States of America 99 (23): 14946–14951.CrossRefGoogle Scholar
  7. 7.
    Boeda, B., et al. 2002. Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle. EMBO Journal 21 (24): 6689–6699.CrossRefGoogle Scholar
  8. 8.
    Weil, D., et al. 2003. Usher syndrome type I G (USH1G) is caused by mutations in the gene encoding SANS, a protein that associates with the USH1C protein, harmonin. Human Molecular Genetics 12 (5): 463–471.CrossRefGoogle Scholar
  9. 9.
    Johnson, K.R., et al. 2003. Mouse models of USH1C and DFNB18: phenotypic and molecular analyses of two new spontaneous mutations of the Ush1c gene. Human Molecular Genetics 12 (23): 3075–3086.CrossRefGoogle Scholar
  10. 10.
    Lefevre, G., et al. 2008. A core cochlear phenotype in USH1 mouse mutants implicates fibrous links of the hair bundle in its cohesion, orientation and differential growth. Development 135 (8): 1427–1437.CrossRefGoogle Scholar
  11. 11.
    Grillet, N., et al. 2009. Harmonin mutations cause mechanotransduction defects in cochlear hair cells. Neuron 62 (3): 375–387.CrossRefGoogle Scholar
  12. 12.
    Michalski, N., et al. 2009. Harmonin-b, an actin-binding scaffold protein, is involved in the adaptation of mechanoelectrical transduction by sensory hair cells. Pflügers Archiv – European Journal of Physiology 459 (1): 115–130.CrossRefGoogle Scholar
  13. 13.
    Pan, L.F., et al. 2009. Assembling stable hair cell tip link complex via multidentate interactions between harmonin and cadherin 23. Proceedings of the National Academy of Sciences of the United States of America 106 (14): 5575–5580.CrossRefGoogle Scholar
  14. 14.
    Alagramam, K.N., et al. 2001. The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene. Nature Genetics 27 (1): 99–102.CrossRefGoogle Scholar
  15. 15.
    Osako, S., and D.A. Hilding. 1971. Electron microscopic studies of capillary permeability in normal and Ames Waltzer deaf mice. Acta Oto-Laryngologica 71 (5): 365–376.CrossRefGoogle Scholar
  16. 16.
    Ahmed, Z.M., et al. 2001. Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F. American Journal of Human Genetics 69 (1): 25–34.CrossRefGoogle Scholar
  17. 17.
    Alagramam, K.N., et al. 2001. Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F. Human Molecular Genetics 10 (16): 1709–1718.CrossRefGoogle Scholar
  18. 18.
    Ben-Yosef, T., et al. 2003. Brief report – a mutation of PCDH15 among Ashkenazi Jews with the type 1 Usher syndrome. New England Journal of Medicine 348 (17): 1664–1670.CrossRefGoogle Scholar
  19. 19.
    Ahmed, Z.M., et al. 2003. PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23. Human Molecular Genetics 12 (24): 3215–3223.CrossRefGoogle Scholar
  20. 20.
    ———. 2006. The tip-link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15. The Journal of Neuroscience 26 (26): 7022–7034.CrossRefGoogle Scholar
  21. 21.
    Kazmierczak, P., et al. 2007. Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells. Nature 449 (7158): 87–91.CrossRefGoogle Scholar
  22. 22.
    Webb, S.W., et al. 2011. Regulation of PCDH15 function in mechanosensory hair cells by alternative splicing of the cytoplasmic domain. Development 138 (8): 1607–1617.CrossRefGoogle Scholar
  23. 23.
    Xiong, W., et al. 2012. TMHS is an integral component of the mechanotransduction machinery of cochlear hair cells. Cell 151 (6): 1283–1295.CrossRefGoogle Scholar
  24. 24.
    Zhao, B., et al. 2014. TMIE is an essential component of the mechanotransduction machinery of cochlear hair cells. Neuron 84 (5): 954–967.CrossRefGoogle Scholar
  25. 25.
    Cunningham, C.L., et al. 2017. The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells. Elife 6: e24318.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Maeda, R., et al. 2014. Tip-link protein protocadherin 15 interacts with transmembrane channel-like proteins TMC1 and TMC2. Proceedings of the National Academy of Sciences of the United States of America 111 (35): 12907–12912.CrossRefGoogle Scholar
  27. 27.
    ———. 2017. Functional analysis of the transmembrane and cytoplasmic domains of Pcdh15a in zebrafish hair cells. The Journal of Neuroscience 37 (12): 3231–3245.CrossRefGoogle Scholar
  28. 28.
    Von Bekesy, G. 1947. The variation of phase along the basilar membrane with sinusoidal vibrations. Journal of the Acoustical Society of America 19 (3): 452–460.CrossRefGoogle Scholar
  29. 29.
    Gold, T. 1948. Hearing. 2. The physical basis of the action of the cochlea. Proceedings of the Royal Society Series B-Biological Sciences 135 (881): 492–498.CrossRefGoogle Scholar
  30. 30.
    Gold, T., and R.J. Pumphrey. 1948. Hearing. 1. The cochlea as a frequency analyzer. Proceedings of the Royal Society Series B-Biological Sciences 135 (881): 462–491.CrossRefGoogle Scholar
  31. 31.
    Rhode, W.S. 1971. Observations of vibration of basilar membrane in squirrel monkeys using Mossbauer technique. Journal of the Acoustical Society of America 49 (4): 1218.CrossRefGoogle Scholar
  32. 32.
    Kemp, D.T. 1978. Stimulated acoustic emissions from within human auditory-system. Journal of the Acoustical Society of America 64 (5): 1386–1391.CrossRefGoogle Scholar
  33. 33.
    Brownell, W.E., et al. 1985. Evoked mechanical responses of isolated cochlear outer hair cells. Science 227 (4683): 194–196.CrossRefGoogle Scholar
  34. 34.
    Zheng, J., et al. 2000. Prestin is the motor protein of cochlear outer hair cells. Nature 405 (6783): 149–155.CrossRefGoogle Scholar
  35. 35.
    Evans, E.F. 1972. The frequency response and other properties of single fibres in the guinea-pig cochlear nerve. The Journal of Physiology 226 (1): 263–287.CrossRefGoogle Scholar
  36. 36.
    Russell, I.J., and P.M. Sellick. 1977. Tuning properties of cochlear hair cells. Nature 267 (5614): 858–860.CrossRefGoogle Scholar
  37. 37.
    ———. 1978. Intracellular studies of hair cells in the mammalian cochlea. The Journal of Physiology 284: 261–290.CrossRefGoogle Scholar
  38. 38.
    Dallos, P. 1992. The active cochlea. The Journal of Neuroscience 12 (12): 4575–4585.CrossRefGoogle Scholar
  39. 39.
    Robles, L., and M.A. Ruggero. 2001. Mechanics of the mammalian cochlea. Physiological Reviews 81 (3): 1305–1352.CrossRefGoogle Scholar
  40. 40.
    Crawford, A.C., and R. Fettiplace. 1981. An electrical tuning mechanism in turtle cochlear hair cells. The Journal of Physiology 312: 377–412.CrossRefGoogle Scholar
  41. 41.
    Art, J.J., and R. Fettiplace. 1987. Variation of Membrane-Properties in Hair-Cells Isolated from the Turtle Cochlea. The Journal of Physiology 385: 207–242.CrossRefGoogle Scholar
  42. 42.
    Hudspeth, A.J., and R.S. Lewis. 1988. A model for electrical resonance and frequency tuning in saccular hair cells of the bull-frog, Rana catesbeiana. The Journal of Physiology 400: 275–297.CrossRefGoogle Scholar
  43. 43.
    Crawford, A.C., and R. Fettiplace. 1980. The frequency selectivity of auditory nerve fibres and hair cells in the cochlea of the turtle. The Journal of Physiology 306: 79–125.CrossRefGoogle Scholar
  44. 44.
    Tucker, T.R., and R. Fettiplace. 1996. Monitoring calcium in turtle hair cells with a calcium-activated potassium channel. The Journal of Physiology 494 (Pt 3): 613–626.CrossRefGoogle Scholar
  45. 45.
    Navaratnam, D.S., et al. 1997. Differential distribution of Ca2+-activated K+ channel splice variants among hair cells along the tonotopic axis of the chick cochlea. Neuron 19 (5): 1077–1085.CrossRefGoogle Scholar
  46. 46.
    Ramanathan, K., et al. 1999. A molecular mechanism for electrical tuning of cochlear hair cells. Science 283 (5399): 215–217.CrossRefGoogle Scholar
  47. 47.
    Oliver, D., et al. 2006. The role of BKCa channels in electrical signal encoding in the mammalian auditory periphery. The Journal of Neuroscience 26 (23): 6181–6189.CrossRefGoogle Scholar
  48. 48.
    Pyott, S.J., et al. 2007. Cochlear function in mice lacking the BK channel alpha, beta1, or beta4 subunits. The Journal of Biological Chemistry 282 (5): 3312–3324.CrossRefGoogle Scholar
  49. 49.
    Ricci, A.J., A.C. Crawford, and R. Fettiplace. 2003. Tonotopic variation in the conductance of the hair cell mechanotransducer channel. Neuron 40 (5): 983–990.CrossRefGoogle Scholar
  50. 50.
    He, D.Z., S. Jia, and P. Dallos. 2004. Mechanoelectrical transduction of adult outer hair cells studied in a gerbil hemicochlea. Nature 429 (6993): 766–770.CrossRefGoogle Scholar
  51. 51.
    Beurg, M., et al. 2006. A large-conductance calcium-selective mechanotransducer channel in mammalian cochlear hair cells. The Journal of Neuroscience 26 (43): 10992–11000.CrossRefGoogle Scholar
  52. 52.
    Ricci, A.J., et al. 2005. The transduction channel filter in auditory hair cells. The Journal of Neuroscience 25 (34): 7831–7839.CrossRefGoogle Scholar
  53. 53.
    Beurg, M., K.X. Kim, and R. Fettiplace. 2014. Conductance and block of hair-cell mechanotransducer channels in transmembrane channel-like protein mutants. The Journal of General Physiology 144 (1): 55–69.CrossRefGoogle Scholar
  54. 54.
    Beurg, M., A.C. Goldring, and R. Fettiplace. 2015. The effects of Tmc1 Beethoven mutation on mechanotransducer channel function in cochlear hair cells. The Journal of General Physiology 146 (3): 233–243.CrossRefGoogle Scholar
  55. 55.
    Beurg, M., et al. 2015. Subunit determination of the conductance of hair-cell mechanotransducer channels. Proceedings of the National Academy of Sciences of the United States of America 112 (5): 1589–1594.CrossRefGoogle Scholar
  56. 56.
    Holt, J.R., et al. 1999. Functional expression of exogenous proteins in mammalian sensory hair cells infected with adenoviral vectors. Journal of Neurophysiology 81 (4): 1881–1888.CrossRefGoogle Scholar
  57. 57.
    Jero, J., et al. 2001. Cochlear gene delivery through an intact round window membrane in mouse. Human Gene Therapy 12 (5): 539–548.CrossRefGoogle Scholar
  58. 58.
    Gubbels, S.P., et al. 2008. Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer. Nature 455 (7212): 537–541.CrossRefGoogle Scholar
  59. 59.
    Akil, O., et al. 2012. Restoration of hearing in the VGLUT3 knockout mouse using virally mediated gene therapy. Neuron 75 (2): 283–293.CrossRefGoogle Scholar
  60. 60.
    Chen, W., et al. 2012. Restoration of auditory evoked responses by human ES-cell-derived otic progenitors. Nature 490 (7419): 278–282.CrossRefGoogle Scholar
  61. 61.
    Mizutari, K., et al. 2013. Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after acoustic trauma. Neuron 77 (1): 58–69.CrossRefGoogle Scholar
  62. 62.
    Lentz, J.J., et al. 2013. Rescue of hearing and vestibular function by antisense oligonucleotides in a mouse model of human deafness. Nature Medicine 19 (3): 345–350.CrossRefGoogle Scholar
  63. 63.
    Pearson, R.A., et al. 2012. Restoration of vision after transplantation of photoreceptors. Nature 485 (7396): 99–103.CrossRefGoogle Scholar
  64. 64.
    Polosukhina, A., et al. 2012. Photochemical restoration of visual responses in blind mice. Neuron 75 (2): 271–282.CrossRefGoogle Scholar
  65. 65.
    Nelson, C.E., et al. 2016. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science 351 (6271): 403–407.CrossRefGoogle Scholar
  66. 66.
    Long, C., et al. 2016. Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science 351 (6271): 400–403.CrossRefGoogle Scholar
  67. 67.
    Tabebordbar, M., et al. 2016. In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science 351 (6271): 407–411.CrossRefGoogle Scholar
  68. 68.
    Zuris, J.A., et al. 2015. Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo. Nature Biotechnology 33 (1): 73–80.CrossRefGoogle Scholar
  69. 69.
    Landegger, L.D., et al. 2017. A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear. Nature Biotechnology 35 (3): 280–284.CrossRefGoogle Scholar
  70. 70.
    Gao, X., et al. 2017. Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents. Nature 553: 217–221.CrossRefGoogle Scholar
  71. 71.
    Pepermans, E., et al. 2014. The CD2 isoform of protocadherin-15 is an essential component of the tip-link complex in mature auditory hair cells. EMBO Molecular Medicine 6 (7): 984–992.CrossRefGoogle Scholar

Copyright information

© The Author(s) 2018

Authors and Affiliations

  1. 1.School of Life Sciences, IDG/McGovern Institute for Brain ResearchTsinghua UniversityBeijingChina

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