Abstract
Hair cells of the inner ear are exquisite sensors that transform mechanical stimuli from sound and head movements into electrical signals. At the core of hair cell mechanotransduction are tip links, fine protein filaments that pull open transduction channels to initiate a cascade of events leading to sensory perception. Tip links are made of cadherin-23 and protocadherin-15, two atypical members of the cadherin superfamily involved in hereditary deafness and blindness. Here we present structural, computational, and biophysical experiments that reveal unique properties of the tip link extracellular cadherin (EC) repeats. Our crystal structures, simulations, and binding assays show how the tip of protocadherin-15 and some of its variants form a mechanically strong and calcium-dependent heterophilic complex with the cadherin-23 tip. In addition, structures and simulations of protocadherin-15 EC repeats show how non-canonical linker regions may alter protocadherin-15's tertiary structure and elasticity. Overall, our results provide a molecular view of tip link mechanics and identify the molecular determinants of tip link function in vertebrate mechanosensation.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
