GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com


Jump to: navigation, search


You don't have sufficient rights on this wiki to edit tables. Perhaps you need to log in. Changes you make in the Table editor will not be saved back to the wiki

See Help for Help on this wiki. See the documentation for how to use the table editor


Kawashima, Y, Géléoc, GS, Kurima, K, Labay, V, Lelli, A, Asai, Y, Makishima, T, Wu, DK, Della Santina, CC, Holt, JR and Griffith, AJ (2011) Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes. J. Clin. Invest. 121:4796-809


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 (Tmc1(Δ) mice) were deaf and those with a deletion of Tmc2 (Tmc2(Δ) mice) were phenotypically normal, Tmc1(Δ)Tmc2(Δ) 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 Tmc1(Δ)Tmc2(Δ) 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.


PubMed PMC3223072 Online version:10.1172/JCI60405


Animals; Cells, Cultured/drug effects; Cells, Cultured/metabolism; Deafness/genetics; Female; Fluorescent Dyes/metabolism; Genetic Complementation Test; Gentamicins/metabolism; Hair Cells, Auditory, Inner/physiology; Hair Cells, Auditory, Inner/ultrastructure; Hair Cells, Vestibular/physiology; Hair Cells, Vestibular/ultrastructure; Male; Mechanotransduction, Cellular/genetics; Mechanotransduction, Cellular/physiology; Membrane Proteins/deficiency; Membrane Proteins/genetics; Membrane Proteins/physiology; Mice; Mice, Inbred C57BL; Protein Isoforms/biosynthesis; Protein Isoforms/genetics; Protein Isoforms/physiology; Pyridinium Compounds/metabolism; Quaternary Ammonium Compounds/metabolism; RNA, Messenger/biosynthesis; Stereocilia/physiology; Stereocilia/ultrastructure