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

被引:504
作者
Corey D.P. [1 ,2 ]
Garcia-Añoveros J. [4 ]
Holt J.R. [5 ]
Kwan K.Y. [1 ,2 ]
Lin S.-Y. [1 ,6 ]
Vollrath M.A. [1 ,2 ]
Amalfitano A. [8 ]
Cheung E.L.-M. [1 ]
Derfler B.H. [1 ,2 ]
Duggan A. [4 ]
Géléoc G.S.G. [5 ]
Gray P.A. [1 ,3 ]
Hoffman M.P. [9 ]
Rehm H.L. [7 ]
Tamasauskas D. [1 ,2 ]
Zhang D.-S. [1 ,2 ]
机构
[1] Department of Neurobiology, Harvard Medical School, Boston
[2] Howard Hughes Medical Institute, Harvard Medical School, Boston
[3] Dana-Farber Cancer Institute, Boston
[4] Department of Anesthesiology, NW Univ. Institute for Neurosciences, Chicago
[5] Department of Neuroscience, Univ. of Virginia School of Medicine, Charlottesville
[6] Department of Biology, Massachusetts Inst. of Technology, Cambridge
[7] Laboratory for Molecular Medicine, Harvard-Partners Genome Center, Cambridge
[8] Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham
[9] Matrix and Morphogenesis Unit, NIDCR, NIH, Bethesda
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nature03066
中图分类号
学科分类号
摘要
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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页码:723 / 730
页数:7
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