Function and Dysfunction of TMC Channels in Inner Ear Hair Cells | Zendy

David P. Corey | Zendy; Nurunisa Akyuz | Zendy; Jeffrey R. Holt | Zendy

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Function and Dysfunction of TMC Channels in Inner Ear Hair Cells

Author(s) -

David P. Corey,

Nurunisa Akyuz,

Jeffrey R. Holt

Publication year - 2018

Publication title -

cold spring harbor perspectives in medicine

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.853

H-Index - 105

eISSN - 2472-5412

pISSN - 2157-1422

DOI - 10.1101/cshperspect.a033506

Subject(s) - mechanotransduction , hair cell , stereocilia (inner ear) , inner ear , microbiology and biotechnology , ion channel , charybdotoxin , superfamily , chemistry , potassium channel , biology , anatomy , biophysics , genetics , gene , receptor

The TMC1 channel was identified as a protein essential for hearing in mouse and human, and recognized as one of a family of eight such proteins in mammals. The TMC family is part of a superfamily of seven branches, which includes the TMEM16s. Vertebrate hair cells express both TMC1 and TMC2. They are located at the tips of stereocilia and are required for hair cell mechanotransduction. TMC1 assembles as a dimer and its similarity to the TMEM16s has enabled a predicted tertiary structure with an ion conduction pore in each subunit of the dimer. Cysteine mutagenesis of the pore supports the role of TMC1 and TMC2 as the core channel proteins of a larger mechanotransduction complex that includes PCDH15 and LHFPL5, and perhaps TMIE, CIB2 and others.

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