Document Detail


TMHS is an integral component of the mechanotransduction machinery of cochlear hair cells.
MedLine Citation:
PMID:  23217710     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Wei Xiong; Nicolas Grillet; Heather M Elledge; Thomas F J Wagner; Bo Zhao; Kenneth R Johnson; Piotr Kazmierczak; Ulrich Müller
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell     Volume:  151     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-02-06     Revised Date:  2013-12-12    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1283-95     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cadherins / metabolism
Hair Cells, Auditory / metabolism*
Hearing*
Mechanotransduction, Cellular*
Membrane Proteins / genetics,  metabolism*,  ultrastructure
Mice
Mice, Knockout
Protein Precursors / metabolism
Stereocilia / metabolism
Grant Support
ID/Acronym/Agency:
DC005965/DC/NIDCD NIH HHS; DC007704/DC/NIDCD NIH HHS; R01 DC004301/DC/NIDCD NIH HHS; R01 DC005965/DC/NIDCD NIH HHS; R01 DC007704/DC/NIDCD NIH HHS
Chemical
Reg. No./Substance:
0/Cadherins; 0/Membrane Proteins; 0/Pcdh15 protein, mouse; 0/Protein Precursors; 0/Tmhs protein, mouse
Comments/Corrections

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