TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells

David P. Corey; Jaime Garcia-Añoveros; Jeffrey R. Holt; Kelvin Y. Kwan; Shuh Yow Lin; Melissa A. Vollrath; Andrea Amalfitano; Eunice L M Cheung; Bruce H. Derfler; Anne Duggan; Gwénaëlle S G Géléoc; Paul A. Gray; Matthew P. Hoffman; Heidi L. Rehm; Daniel Tamasauskas; Duan Sun Zhang

doi:10.1038/nature03066

TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells

David P. Corey^*, Jaime Garcia-Añoveros, Jeffrey R. Holt, Kelvin Y. Kwan, Shuh Yow Lin, Melissa A. Vollrath, Andrea Amalfitano, Eunice L M Cheung, Bruce H. Derfler, Anne Duggan, Gwénaëlle S G Géléoc, Paul A. Gray, Matthew P. Hoffman, Heidi L. Rehm, Daniel Tamasauskas, Duan Sun Zhang

^*Corresponding author for this work

Anesthesiology

Research output: Contribution to journal › Article › peer-review

579 Scopus citations

Abstract

Mechanical deflection of the sensory hair bundles of receptor cells in the inner ear causes ion channels located at the tips of the bundle to open, thereby initiating the perception of sound. Although some protein constituents of the transduction apparatus are known, the mechanically gated transaction channels have not been identified in higher vertebrates. Here, we investigate TRP (transient receptor potential) ion channels as candidates and find one, TRPA1 (also known as ANKTM1), that meets criteria for the transduction channel. The appearance of TRPA1 messenger RNA expression in hair cell epithelia coincides developmentally with the onset of mechanosensitivity. Antibodies to TRPA1 label hair bundles, especially at their tips, and tip labelling disappears when the transduction apparatus is chemically disrupted, inhibition of TRPA1 protein expression in zebrafish and mouse inner ears inhibits receptor cell function, as assessed with electrical recording and with accumulation of a channel-permeant fluorescent dye. TRPA1 is probably a component of the transduction channel itself.

Original language	English (US)
Pages (from-to)	723-730
Number of pages	8
Journal	Nature
Volume	432
Issue number	7018
DOIs	https://doi.org/10.1038/nature03066
State	Published - Dec 9 2004

Funding

Acknowledgements Authors’ contributions are listed in Supplementary Information. We thank C.-L. Chen and Q. Ma for assistance with in situ hybridization, N. Hopkins for zebrafish support and L. Stevens for laboratory administration. This work was supported by grants from NIH to N. Hopkins, S.-Y.L., J.G.-A., G.S.G.G., J.R.H. and D.P.C.; from the Mathers Foundation to D.P.C.; from the Howard Hughes Medical Institute (J.G.-A.); and from the Charles Dana Foundation to Q. Ma. P.G. was a Parker B. Francis Fellow in Pulmonary Medicine. J.G.-A., A.D., G.G., J.R.H. and H.L.R. were Associates, M.A.V. and K.K. are Associates, and D.P.C. is an Investigator of the Howard Hughes Medical Institute.

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Corey, D. P., Garcia-Añoveros, J., Holt, J. R., Kwan, K. Y., Lin, S. Y., Vollrath, M. A., Amalfitano, A., Cheung, E. L. M., Derfler, B. H., Duggan, A., Géléoc, G. S. G., Gray, P. A., Hoffman, M. P., Rehm, H. L., Tamasauskas, D., & Zhang, D. S. (2004). TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. Nature, 432(7018), 723-730. https://doi.org/10.1038/nature03066

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title = "TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells",

abstract = "Mechanical deflection of the sensory hair bundles of receptor cells in the inner ear causes ion channels located at the tips of the bundle to open, thereby initiating the perception of sound. Although some protein constituents of the transduction apparatus are known, the mechanically gated transaction channels have not been identified in higher vertebrates. Here, we investigate TRP (transient receptor potential) ion channels as candidates and find one, TRPA1 (also known as ANKTM1), that meets criteria for the transduction channel. The appearance of TRPA1 messenger RNA expression in hair cell epithelia coincides developmentally with the onset of mechanosensitivity. Antibodies to TRPA1 label hair bundles, especially at their tips, and tip labelling disappears when the transduction apparatus is chemically disrupted, inhibition of TRPA1 protein expression in zebrafish and mouse inner ears inhibits receptor cell function, as assessed with electrical recording and with accumulation of a channel-permeant fluorescent dye. TRPA1 is probably a component of the transduction channel itself.",

author = "Corey, {David P.} and Jaime Garcia-A{\~n}overos and Holt, {Jeffrey R.} and Kwan, {Kelvin Y.} and Lin, {Shuh Yow} and Vollrath, {Melissa A.} and Andrea Amalfitano and Cheung, {Eunice L M} and Derfler, {Bruce H.} and Anne Duggan and G{\'e}l{\'e}oc, {Gw{\'e}na{\"e}lle S G} and Gray, {Paul A.} and Hoffman, {Matthew P.} and Rehm, {Heidi L.} and Daniel Tamasauskas and Zhang, {Duan Sun}",

note = "Funding Information: Acknowledgements Authors{\textquoteright} contributions are listed in Supplementary Information. We thank C.-L. Chen and Q. Ma for assistance with in situ hybridization, N. Hopkins for zebrafish support and L. Stevens for laboratory administration. This work was supported by grants from NIH to N. Hopkins, S.-Y.L., J.G.-A., G.S.G.G., J.R.H. and D.P.C.; from the Mathers Foundation to D.P.C.; from the Howard Hughes Medical Institute (J.G.-A.); and from the Charles Dana Foundation to Q. Ma. P.G. was a Parker B. Francis Fellow in Pulmonary Medicine. J.G.-A., A.D., G.G., J.R.H. and H.L.R. were Associates, M.A.V. and K.K. are Associates, and D.P.C. is an Investigator of the Howard Hughes Medical Institute.",

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Corey, DP, Garcia-Añoveros, J, Holt, JR, Kwan, KY, Lin, SY, Vollrath, MA, Amalfitano, A, Cheung, ELM, Derfler, BH, Duggan, A, Géléoc, GSG, Gray, PA, Hoffman, MP, Rehm, HL, Tamasauskas, D & Zhang, DS 2004, 'TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells', Nature, vol. 432, no. 7018, pp. 723-730. https://doi.org/10.1038/nature03066

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T1 - TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells

AU - Corey, David P.

AU - Garcia-Añoveros, Jaime

AU - Holt, Jeffrey R.

AU - Kwan, Kelvin Y.

AU - Lin, Shuh Yow

AU - Vollrath, Melissa A.

AU - Amalfitano, Andrea

AU - Cheung, Eunice L M

AU - Derfler, Bruce H.

AU - Duggan, Anne

AU - Géléoc, Gwénaëlle S G

AU - Gray, Paul A.

AU - Hoffman, Matthew P.

AU - Rehm, Heidi L.

AU - Tamasauskas, Daniel

AU - Zhang, Duan Sun

N1 - Funding Information: Acknowledgements Authors’ contributions are listed in Supplementary Information. We thank C.-L. Chen and Q. Ma for assistance with in situ hybridization, N. Hopkins for zebrafish support and L. Stevens for laboratory administration. This work was supported by grants from NIH to N. Hopkins, S.-Y.L., J.G.-A., G.S.G.G., J.R.H. and D.P.C.; from the Mathers Foundation to D.P.C.; from the Howard Hughes Medical Institute (J.G.-A.); and from the Charles Dana Foundation to Q. Ma. P.G. was a Parker B. Francis Fellow in Pulmonary Medicine. J.G.-A., A.D., G.G., J.R.H. and H.L.R. were Associates, M.A.V. and K.K. are Associates, and D.P.C. is an Investigator of the Howard Hughes Medical Institute.

PY - 2004/12/9

Y1 - 2004/12/9

N2 - Mechanical deflection of the sensory hair bundles of receptor cells in the inner ear causes ion channels located at the tips of the bundle to open, thereby initiating the perception of sound. Although some protein constituents of the transduction apparatus are known, the mechanically gated transaction channels have not been identified in higher vertebrates. Here, we investigate TRP (transient receptor potential) ion channels as candidates and find one, TRPA1 (also known as ANKTM1), that meets criteria for the transduction channel. The appearance of TRPA1 messenger RNA expression in hair cell epithelia coincides developmentally with the onset of mechanosensitivity. Antibodies to TRPA1 label hair bundles, especially at their tips, and tip labelling disappears when the transduction apparatus is chemically disrupted, inhibition of TRPA1 protein expression in zebrafish and mouse inner ears inhibits receptor cell function, as assessed with electrical recording and with accumulation of a channel-permeant fluorescent dye. TRPA1 is probably a component of the transduction channel itself.

AB - Mechanical deflection of the sensory hair bundles of receptor cells in the inner ear causes ion channels located at the tips of the bundle to open, thereby initiating the perception of sound. Although some protein constituents of the transduction apparatus are known, the mechanically gated transaction channels have not been identified in higher vertebrates. Here, we investigate TRP (transient receptor potential) ion channels as candidates and find one, TRPA1 (also known as ANKTM1), that meets criteria for the transduction channel. The appearance of TRPA1 messenger RNA expression in hair cell epithelia coincides developmentally with the onset of mechanosensitivity. Antibodies to TRPA1 label hair bundles, especially at their tips, and tip labelling disappears when the transduction apparatus is chemically disrupted, inhibition of TRPA1 protein expression in zebrafish and mouse inner ears inhibits receptor cell function, as assessed with electrical recording and with accumulation of a channel-permeant fluorescent dye. TRPA1 is probably a component of the transduction channel itself.

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JO - Nature

JF - Nature

IS - 7018

ER -

TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells

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