| Literature DB >> 33558532 |
Eric M Mulhall1,2, Andrew Ward1,3, Darren Yang3, Mounir A Koussa1,2, David P Corey4, Wesley P Wong5,6,7.
Abstract
The conversion of auditory and vestibular stimuli into electrical signals is initiated by force transmitted to a mechanotransduction channel through the tip link, a double stranded protein filament held together by two adhesion bonds in the middle. Although thought to form a relatively static structure, the dynamics of the tip-link connection has not been measured. Here, we biophysically characterize the strength of the tip-link connection at single-molecule resolution. We show that a single tip-link bond is more mechanically stable relative to classic cadherins, and our data indicate that the double stranded tip-link connection is stabilized by single strand rebinding facilitated by strong cis-dimerization domains. The measured lifetime of seconds suggests the tip-link is far more dynamic than previously thought. We also show how Ca2+ alters tip-link lifetime through elastic modulation and reveal the mechanical phenotype of a hereditary deafness mutation. Together, these data show how the tip link is likely to function during mechanical stimuli.Entities:
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Year: 2021 PMID： 33558532 PMCID： PMC7870652 DOI： 10.1038/s41467-021-21033-6
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919