Nanomechanics of tip-link cadherins

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...

Descripción completa

Detalles Bibliográficos
Autores: Oroz, Javier, Galera-Prat, Albert, Hervás, Rubén, Valbuena Jiménez, Alejandro, Fernández-Bravo, Débora, Carrión-Vázquez, Mariano
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/690981
Acceso en línea:http://hdl.handle.net/10486/690981
https://dx.doi.org/10.1038/s41598-019-49518-x
Access Level:acceso abierto
Palabra clave:hearing
cadherin 23
protocadherin 15
deafness
Biología y Biomedicina / Biología
id ES_5baef7390c24f5ff50c8e6ec340d9ec0
oai_identifier_str oai:repositorio.uam.es:10486/690981
network_acronym_str ES
network_name_str España
repository_id_str
spelling Nanomechanics of tip-link cadherinsOroz, JavierGalera-Prat, AlbertHervás, RubénValbuena Jiménez, AlejandroFernández-Bravo, DéboraCarrión-Vázquez, Marianohearingcadherin 23protocadherin 15deafnessBiología y Biomedicina / BiologíaHearing 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 cadherinsThis work was supported by the BIO2010-22275 grant from the Spanish Ministry of Science and Innovation (MICINN) to M.C.-V.Nature Research (part of Springer Nature)Departamento de Biología MolecularFacultad de Ciencias20192019-09-16research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/690981https://dx.doi.org/10.1038/s41598-019-49518-xreponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6909812026-06-23T12:46:27Z
dc.title.none.fl_str_mv Nanomechanics of tip-link cadherins
title Nanomechanics of tip-link cadherins
spellingShingle Nanomechanics of tip-link cadherins
Oroz, Javier
hearing
cadherin 23
protocadherin 15
deafness
Biología y Biomedicina / Biología
title_short Nanomechanics of tip-link cadherins
title_full Nanomechanics of tip-link cadherins
title_fullStr Nanomechanics of tip-link cadherins
title_full_unstemmed Nanomechanics of tip-link cadherins
title_sort Nanomechanics of tip-link cadherins
dc.creator.none.fl_str_mv Oroz, Javier
Galera-Prat, Albert
Hervás, Rubén
Valbuena Jiménez, Alejandro
Fernández-Bravo, Débora
Carrión-Vázquez, Mariano
author Oroz, Javier
author_facet Oroz, Javier
Galera-Prat, Albert
Hervás, Rubén
Valbuena Jiménez, Alejandro
Fernández-Bravo, Débora
Carrión-Vázquez, Mariano
author_role author
author2 Galera-Prat, Albert
Hervás, Rubén
Valbuena Jiménez, Alejandro
Fernández-Bravo, Débora
Carrión-Vázquez, Mariano
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv hearing
cadherin 23
protocadherin 15
deafness
Biología y Biomedicina / Biología
topic hearing
cadherin 23
protocadherin 15
deafness
Biología y Biomedicina / Biología
description 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
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-09-16
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/690981
https://dx.doi.org/10.1038/s41598-019-49518-x
url http://hdl.handle.net/10486/690981
https://dx.doi.org/10.1038/s41598-019-49518-x
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Research (part of Springer Nature)
publisher.none.fl_str_mv Nature Research (part of Springer Nature)
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869408820015398912
score 15.301603

Similares en LA Referencia