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Function and Dysfunction of TMC Channels in Inner Ear Hair Cells
David P Corey1, Nurunisa Akyuz1, Jeffrey R Holt2
1Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
Cold Spring Harbor Perspectives in Medicine
|October 7, 2018
Summary
The TMC1 channel protein is crucial for hearing in mammals. Research shows it forms part of a larger complex essential for mechanotransduction in hair cells.
Area of Science:
- * Molecular Biology
- * Neuroscience
- * Genetics
Background:
- * The TMC1 channel is a protein vital for hearing in mice and humans.
- * It belongs to a family of eight mammalian proteins and is part of the larger TMEM16 superfamily.
- * TMC1 and TMC2 are expressed in vertebrate hair cells, located at stereocilia tips, and are essential for mechanotransduction.
Purpose of the Study:
- * To elucidate the structural and functional role of the TMC1 channel in hearing.
- * To understand the composition of the mechanotransduction complex in hair cells.
Main Methods:
- * Analysis of TMC1 protein structure and function.
- * Cysteine mutagenesis of the ion conduction pore.
- * Investigating the interaction of TMC1 with other proteins in the mechanotransduction complex.
Main Results:
- * TMC1 forms a dimer with a predicted ion conduction pore, similar to TMEM16 proteins.
- * Cysteine mutagenesis data supports TMC1 and TMC2 as core components of the mechanotransduction channel.
- * Identified TMC1 and TMC2 as central to a complex involving PCDH15, LHFPL5, and potentially TMIE and CIB2.
Conclusions:
- * TMC1 and TMC2 are the primary ion channel proteins responsible for mechanotransduction in hair cells.
- * These channels are integral to a multi-protein complex essential for the process of hearing.
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