Molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells.

Sound detection by inner ear hair cells requires tip links that interconnect mechanosensory stereocilia and convey force to yet unidentified transduction channels. Current models postulate a static composition of the tip link, with protocadherin 15 (PCDH15) at the lower and cadherin 23 (CDH23) at th...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Artur A Indzhykulian, Ruben Stepanyan, Anastasiia Nelina, Kateri J Spinelli, Zubair M Ahmed, Inna A Belyantseva, Thomas B Friedman, Peter G Barr-Gillespie, Gregory I Frolenkov
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/dce20030d1bd4f91a84ae8fa5707710a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:dce20030d1bd4f91a84ae8fa5707710a
record_format	dspace
spelling	oai:doaj.org-article:dce20030d1bd4f91a84ae8fa5707710a2021-11-18T05:37:03ZMolecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells.1544-91731545-788510.1371/journal.pbio.1001583https://doaj.org/article/dce20030d1bd4f91a84ae8fa5707710a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23776407/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Sound detection by inner ear hair cells requires tip links that interconnect mechanosensory stereocilia and convey force to yet unidentified transduction channels. Current models postulate a static composition of the tip link, with protocadherin 15 (PCDH15) at the lower and cadherin 23 (CDH23) at the upper end of the link. In terminally differentiated mammalian auditory hair cells, tip links are subjected to sound-induced forces throughout an organism's life. Although hair cells can regenerate disrupted tip links and restore hearing, the molecular details of this process are unknown. We developed a novel implementation of backscatter electron scanning microscopy to visualize simultaneously immuno-gold particles and stereocilia links, both of only a few nanometers in diameter. We show that functional, mechanotransduction-mediating tip links have at least two molecular compositions, containing either PCDH15/CDH23 or PCDH15/PCDH15. During regeneration, shorter tip links containing nearly equal amounts of PCDH15 at both ends appear first. Whole-cell patch-clamp recordings demonstrate that these transient PCDH15/PCDH15 links mediate mechanotransduction currents of normal amplitude but abnormal Ca(2+)-dependent decay (adaptation). The mature PCDH15/CDH23 tip link composition is re-established later, concomitant with complete recovery of adaptation. Thus, our findings provide a molecular mechanism for regeneration and maintenance of mechanosensory function in postmitotic auditory hair cells and could help identify elusive components of the mechanotransduction machinery.Artur A IndzhykulianRuben StepanyanAnastasiia NelinaKateri J SpinelliZubair M AhmedInna A BelyantsevaThomas B FriedmanPeter G Barr-GillespieGregory I FrolenkovPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 11, Iss 6, p e1001583 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Artur A Indzhykulian Ruben Stepanyan Anastasiia Nelina Kateri J Spinelli Zubair M Ahmed Inna A Belyantseva Thomas B Friedman Peter G Barr-Gillespie Gregory I Frolenkov Molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells.
description	Sound detection by inner ear hair cells requires tip links that interconnect mechanosensory stereocilia and convey force to yet unidentified transduction channels. Current models postulate a static composition of the tip link, with protocadherin 15 (PCDH15) at the lower and cadherin 23 (CDH23) at the upper end of the link. In terminally differentiated mammalian auditory hair cells, tip links are subjected to sound-induced forces throughout an organism's life. Although hair cells can regenerate disrupted tip links and restore hearing, the molecular details of this process are unknown. We developed a novel implementation of backscatter electron scanning microscopy to visualize simultaneously immuno-gold particles and stereocilia links, both of only a few nanometers in diameter. We show that functional, mechanotransduction-mediating tip links have at least two molecular compositions, containing either PCDH15/CDH23 or PCDH15/PCDH15. During regeneration, shorter tip links containing nearly equal amounts of PCDH15 at both ends appear first. Whole-cell patch-clamp recordings demonstrate that these transient PCDH15/PCDH15 links mediate mechanotransduction currents of normal amplitude but abnormal Ca(2+)-dependent decay (adaptation). The mature PCDH15/CDH23 tip link composition is re-established later, concomitant with complete recovery of adaptation. Thus, our findings provide a molecular mechanism for regeneration and maintenance of mechanosensory function in postmitotic auditory hair cells and could help identify elusive components of the mechanotransduction machinery.
format	article
author	Artur A Indzhykulian Ruben Stepanyan Anastasiia Nelina Kateri J Spinelli Zubair M Ahmed Inna A Belyantseva Thomas B Friedman Peter G Barr-Gillespie Gregory I Frolenkov
author_facet	Artur A Indzhykulian Ruben Stepanyan Anastasiia Nelina Kateri J Spinelli Zubair M Ahmed Inna A Belyantseva Thomas B Friedman Peter G Barr-Gillespie Gregory I Frolenkov
author_sort	Artur A Indzhykulian
title	Molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells.
title_short	Molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells.
title_full	Molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells.
title_fullStr	Molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells.
title_full_unstemmed	Molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells.
title_sort	molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/dce20030d1bd4f91a84ae8fa5707710a
work_keys_str_mv	AT arturaindzhykulian molecularremodelingoftiplinksunderliesmechanosensoryregenerationinauditoryhaircells AT rubenstepanyan molecularremodelingoftiplinksunderliesmechanosensoryregenerationinauditoryhaircells AT anastasiianelina molecularremodelingoftiplinksunderliesmechanosensoryregenerationinauditoryhaircells AT katerijspinelli molecularremodelingoftiplinksunderliesmechanosensoryregenerationinauditoryhaircells AT zubairmahmed molecularremodelingoftiplinksunderliesmechanosensoryregenerationinauditoryhaircells AT innaabelyantseva molecularremodelingoftiplinksunderliesmechanosensoryregenerationinauditoryhaircells AT thomasbfriedman molecularremodelingoftiplinksunderliesmechanosensoryregenerationinauditoryhaircells AT petergbarrgillespie molecularremodelingoftiplinksunderliesmechanosensoryregenerationinauditoryhaircells AT gregoryifrolenkov molecularremodelingoftiplinksunderliesmechanosensoryregenerationinauditoryhaircells
_version_	1718424883986169856

Molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells.

Ejemplares similares