Nanomechanics of tip-link cadherins
Entity
UAM. Departamento de Biología MolecularPublisher
Nature Research (part of Springer Nature)Date
2019-09-16Citation
10.1038/s41598-019-49518-x
Sci Rep 9 (2019): 13306
ISSN
2045-2322DOI
10.1038/s41598-019-49518-xFunded by
This work was supported by the BIO2010-22275 grant from the Spanish Ministry of Science and Innovation (MICINN) to M.C.-V.Project
Gobierno de España. BIO2010-22275Editor's Version
https://doi.org/10.1038/s41598-019-49518-xSubjects
hearing; cadherin 23; protocadherin 15; deafness; Biología y Biomedicina / BiologíaRights
© The Author(s) 2019Abstract
Hearing and balance rely on the transduction of mechanical stimuli arising from sound waves or head movements into electrochemical signals. This archetypal mechanoelectrical transduction process occurs in the hair-cell stereocilia of the inner ear, which experience continuous oscillations driven by undulations in the endolymph in which they are immersed. The filamentous structures called tip links, formed by an intertwined thread composed of an heterotypic complex of cadherin 23 and protocadherin 15 ectodomain dimers, connect each stereocilium to the tip of the lower sterocilium, and must maintain their integrity against continuous stimulatory deflections. By using single molecule force spectroscopy, here we demonstrate that in contrast to the case of classical cadherins, tip-link cadherins are mechanoresilient structures even at the exceptionally low Ca2+ concentration of the endolymph. We also show that the D101G deafness point mutation in cadherin 23, which affects a Ca2+ coordination site, exhibits an altered mechanical phenotype at the physiological Ca2+ concentration. Our results show a remarkable case of functional adaptation of a protein’s nanomechanics to extremely low Ca2+ concentrations and pave the way to a full understanding of the mechanotransduction mechanism mediated by auditory cadherins
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Google Scholar:Oroz, Javier
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Galera-Prat, Albert
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Hervás, Rubén
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Valbuena, Alejandro
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Fernández-Bravo, Débora
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Carrión-Vázquez, Mariano
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