Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes

Yoshiyuki Kawashima, Gwenaëlle S G Géléoc, Kiyoto Kurima, Valentina Labay, Andrea Lelli, Yukako Asai, Tomoko Makishima, Doris K. Wu, Charles C. Della Santina, Jeffrey R. Holt, Andrew J. Griffith

Research output: Contribution to journalArticle

183 Citations (Scopus)

Abstract

Inner ear hair cells convert the mechanical stimuli of sound, gravity, and head movement into electrical signals. This mechanotransduction process is initiated by opening of cation channels near the tips of hair cell stereocilia. Since the identity of these ion channels is unknown, and mutations in the gene encoding transmembrane channel-like 1 (TMC1) cause hearing loss without vestibular dysfunction in both mice and humans, we investigated the contribution of Tmc1 and the closely related Tmc2 to mechanotransduction in mice. We found that Tmc1 and Tmc2 were expressed in mouse vestibular and cochlear hair cells and that GFP-tagged TMC proteins localized near stereocilia tips. Tmc2 expression was transient in early postnatal mouse cochlear hair cells but persisted in vestibular hair cells. While mice with a targeted deletion of Tmc1 (Tmc1Δ mice) were deaf and those with a deletion of Tmc2 (Tmc2Δ mice) were phenotypically normal, Tmc1ΔTmc2Δ mice had profound vestibular dysfunction, deafness, and structurally normal hair cells that lacked all mechanotransduction activity. Expression of either exogenous TMC1 or TMC2 rescued mechanotransduction in Tmc1ΔTmc2Δ mutant hair cells. Our results indicate that TMC1 and TMC2 are necessary for hair cell mechanotransduction and may be integral components of the mechanotransduction complex. Our data also suggest that persistent TMC2 expression in vestibular hair cells may preserve vestibular function in humans with hearing loss caused by TMC1 mutations.

Original languageEnglish (US)
Pages (from-to)4796-4809
Number of pages14
JournalJournal of Clinical Investigation
Volume121
Issue number12
DOIs
StatePublished - Dec 1 2011

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Inner Auditory Hair Cells
Inner Ear
Vestibular Hair Cells
Genes
Auditory Hair Cells
Stereocilia
Hearing Loss
Head Movements
Mutation
Gravitation
Deafness
Ion Channels
Cations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kawashima, Y., Géléoc, G. S. G., Kurima, K., Labay, V., Lelli, A., Asai, Y., ... Griffith, A. J. (2011). Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes. Journal of Clinical Investigation, 121(12), 4796-4809. https://doi.org/10.1172/JCI60405

Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes. / Kawashima, Yoshiyuki; Géléoc, Gwenaëlle S G; Kurima, Kiyoto; Labay, Valentina; Lelli, Andrea; Asai, Yukako; Makishima, Tomoko; Wu, Doris K.; Della Santina, Charles C.; Holt, Jeffrey R.; Griffith, Andrew J.

In: Journal of Clinical Investigation, Vol. 121, No. 12, 01.12.2011, p. 4796-4809.

Research output: Contribution to journalArticle

Kawashima, Y, Géléoc, GSG, Kurima, K, Labay, V, Lelli, A, Asai, Y, Makishima, T, Wu, DK, Della Santina, CC, Holt, JR & Griffith, AJ 2011, 'Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes', Journal of Clinical Investigation, vol. 121, no. 12, pp. 4796-4809. https://doi.org/10.1172/JCI60405
Kawashima, Yoshiyuki ; Géléoc, Gwenaëlle S G ; Kurima, Kiyoto ; Labay, Valentina ; Lelli, Andrea ; Asai, Yukako ; Makishima, Tomoko ; Wu, Doris K. ; Della Santina, Charles C. ; Holt, Jeffrey R. ; Griffith, Andrew J. / Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes. In: Journal of Clinical Investigation. 2011 ; Vol. 121, No. 12. pp. 4796-4809.
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