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.
journal_name
Celljournal_title
Cellauthors
Xiong W,Grillet N,Elledge HM,Wagner TF,Zhao B,Johnson KR,Kazmierczak P,Müller Udoi
10.1016/j.cell.2012.10.041subject
Has Abstractpub_date
2012-12-07 00:00:00pages
1283-95issue
6eissn
0092-8674issn
1097-4172pii
S0092-8674(12)01304-9journal_volume
151pub_type
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