TMIE is an Essential Component of the Mechanotransduction Machinery of Cochlear Hair Cells

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2014 Dec 4

PMID 25467981

Citations 135

Authors

Bo Zhao

Zizhen Wu

Nicolas Grillet

Linxuan Yan

Wei Xiong

Sarah Harkins-Perry

Ulrich Muller

Affiliations

Soon will be listed here.

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.

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