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Neuron. 2014 Dec 3;84(5):954-67. doi: 10.1016/j.neuron.2014.10.041. Epub 2014 Nov 20.

TMIE is an essential component of the mechanotransduction machinery of cochlear hair cells.

Author information

1
Dorris Neuroscience Center, Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
2
Dorris Neuroscience Center, Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: umueller@scripps.edu.

Abstract

Hair cells are the mechanosensory cells of the inner ear. Mechanotransduction channels in hair cells are gated by tip links. The molecules that connect tip links to transduction channels are not known. Here we show that the transmembrane protein TMIE forms a ternary complex with the tip-link component PCDH15 and its binding partner TMHS/LHFPL5. Alternative splicing of the PCDH15 cytoplasmic domain regulates formation of this ternary complex. Transducer currents are abolished by a homozygous Tmie-null mutation, and subtle Tmie mutations that disrupt interactions between TMIE and tip links affect transduction, suggesting that TMIE is an essential component of the hair cell's mechanotransduction machinery that functionally couples the tip link to the transduction channel. The multisubunit composition of the transduction complex and the regulation of complex assembly by alternative splicing is likely critical for regulating channel properties in different hair cells and along the cochlea's tonotopic axis.

PMID:
25467981
PMCID:
PMC4258123
DOI:
10.1016/j.neuron.2014.10.041
[Indexed for MEDLINE]
Free PMC Article

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