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Transmembrane channel-like (TMC) genes are required for auditory and vestibular mechanosensation

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Abstract

Mutations of the transmembrane channel-like 1 (TMC1) gene can cause dominant and recessive forms of deafness in humans and mice. TMC1 is one of eight mammalian TMC genes of unknown function. The multi-pass transmembrane topologic structure of the proteins they encode suggests roles as a receptor, transporter, channel, or pump. Tmc1 and the closely related Tmc2 gene are expressed in neurosensory hair cells of the auditory and vestibular end organs of the mouse inner ear. Recent studies have demonstrated that Tmc1 and Tmc2 are specifically required for mechanoelectrical transduction in hair cells. The exact role of these proteins in mechanoelectrical transduction is unknown. TMC1 and TMC2 are viable candidates for the mechanoelectrical transduction channel of hair cells, whose component molecules have eluded identification for over 30 years. We expect that studies of TMC proteins will yield insights into molecular components and mechanisms of mechanosensation in auditory and vestibular hair cells, as well as in other tissues and organs.

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Acknowledgments

Kiyoto Kurima and Andrew Griffith are supported by NIH intramural research fund Z01-DC000060-13. Bifeng Pan and Jeffrey R. Holt are supported by NIH/NIDCD grant no. RO1DC013521. Yoshiyuki Kawashima is supported by JSPS KAKENHI grant no. 26462551.

Conflict of interest

Kiyoto Kurima and Andrew J. Griffith hold the following U.S. patents: 7,166,433 (Transductin-2 and Applications to Hereditary Deafness), 7,192,705 (Transductin-1 and Applications to Hereditary Deafness), and 7,659,115 (Nucleic Acid Encoding Human Transductin-1 Polypeptide).

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Authors and Affiliations

  1. Department of Otolaryngology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan

    Yoshiyuki Kawashima

  2. Molecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health, 35A Convent Drive, Room GF-103, Bethesda, MD, 20892, USA

    Kiyoto Kurima & Andrew J. Griffith

  3. Department of Otolaryngology, F.M. Kirby Neurobiology Center, Boston Children’s Hospital and Harvard Medical School, 300 Longwood Ave, CLS 12251, Boston, MA, 02115, USA

    Bifeng Pan & Jeffrey R. Holt

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  1. Yoshiyuki Kawashima
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Correspondence to Andrew J. Griffith or Jeffrey R. Holt.

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Kawashima, Y., Kurima, K., Pan, B. et al. Transmembrane channel-like (TMC) genes are required for auditory and vestibular mechanosensation. Pflugers Arch - Eur J Physiol 467, 85–94 (2015). https://doi.org/10.1007/s00424-014-1582-3

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  • DOI: https://doi.org/10.1007/s00424-014-1582-3

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