TMHS is an Integral Component of the Mechanotransduction Machinery of Cochlear Hair Cells

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2012 Dec 11

PMID 23217710

Citations 156

Authors

Wei Xiong

Nicolas Grillet

Heather M Elledge

Thomas F J Wagner

Bo Zhao

Kenneth R Johnson

Piotr Kazmierczak

Ulrich Muller

Affiliations

Soon will be listed here.

Abstract

Hair cells are mechanosensors for the perception of sound, acceleration, and fluid motion. Mechanotransduction channels in hair cells are gated by tip links, which connect the stereocilia of a hair cell in the direction of their mechanical sensitivity. The molecular constituents of the mechanotransduction channels of hair cells are not known. Here, we show that mechanotransduction is impaired in mice lacking the tetraspan TMHS. TMHS binds to the tip-link component PCDH15 and regulates tip-link assembly, a process that is disrupted by deafness-causing Tmhs mutations. TMHS also regulates transducer channel conductance and is required for fast channel adaptation. TMHS therefore resembles other ion channel regulatory subunits such as the transmembrane alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor regulatory proteins (TARPs) of AMPA receptors that facilitate channel transport and regulate the properties of pore-forming channel subunits. We conclude that TMHS is an integral component of the hair cell's mechanotransduction machinery that functionally couples PCDH15 to the transduction channel.

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