Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses

Autores
Michalski, Nicolas; Goutman, Juan Diego; Auclair, Sarah Marie; Boutet de Monvel, Jaques; Tertrais, margot; Emptoz, Alice; Parrin, Alexandre; Nouaille, Sylvie; Guillon, Marc; Sachse, Martin; Ciric, Danica; Bahloul, Amel; Hardelin, Jean Pierre; Sutton, Roger Bryan; Avan, Paul; Krishnakumar, Shyam S.; Rothman, James E.; Dulon, Didier; Safieddine, Saaid; Petit, Christine
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hearing relies on rapid, temporally precise, and sustained neurotransmitter release at the ribbon synapses of sensory cells, the inner hair cells (IHCs). This process requires otoferlin, a six C2-domain, Ca2+-binding transmembrane protein of synaptic vesicles. To decipher the role of otoferlin in the synaptic vesicle cycle, we produced knock-in mice (Otof Ala515,Ala517/Ala515,Ala517) with lower Ca2+-binding affinity of the C2C domain. The IHC ribbon synapse structure, synaptic Ca2+ currents, and otoferlin distribution were unaffected in these mutant mice, but auditory brainstem response wave-I amplitude was reduced. Lower Ca2+ sensitivity and delay of the fast and sustained components of synaptic exocytosis were revealed by membrane capacitance measurement upon modulations of intracellular Ca2+ concentration, by varying Ca2+ influx through voltage-gated Ca2+-channels or Ca2+ uncaging. Otoferlin thus functions as a Ca2+ sensor, setting the rates of primed vesicle fusion with the presynaptic plasma membrane and synaptic vesicle pool replenishment in the IHC active zone.
Fil: Michalski, Nicolas. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia
Fil: Goutman, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Auclair, Sarah Marie. University of Yale; Estados Unidos
Fil: Boutet de Monvel, Jaques. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia
Fil: Tertrais, margot. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Bordeaux; Francia
Fil: Emptoz, Alice. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia
Fil: Parrin, Alexandre. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia
Fil: Nouaille, Sylvie. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia
Fil: Guillon, Marc. Centre National de la Recherche Scientifique; Francia. University Paris Descartes; Francia
Fil: Sachse, Martin. Instituto Pasteur; Francia
Fil: Ciric, Danica. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia
Fil: Bahloul, Amel. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Hardelin, Jean Pierre. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia
Fil: Sutton, Roger Bryan. Texas Tech University; Estados Unidos
Fil: Avan, Paul. Université Clermont Auvergne; Francia. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Krishnakumar, Shyam S.. University of Yale; Estados Unidos
Fil: Rothman, James E.. University of Yale; Estados Unidos. University College London; Reino Unido
Fil: Dulon, Didier. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Bordeaux; Francia
Fil: Safieddine, Saaid. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia. Centre National de la Recherche Scientifique; Francia. University College London; Reino Unido
Fil: Petit, Christine. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia. Institut de la Vision; Francia
Materia
deafness
neurotransmitter release
synaptic exocytotic machinery
synaptopathy
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/70927
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/70927
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapsesMichalski, NicolasGoutman, Juan DiegoAuclair, Sarah MarieBoutet de Monvel, JaquesTertrais, margotEmptoz, AliceParrin, AlexandreNouaille, SylvieGuillon, MarcSachse, MartinCiric, DanicaBahloul, AmelHardelin, Jean PierreSutton, Roger BryanAvan, PaulKrishnakumar, Shyam S.Rothman, James E.Dulon, DidierSafieddine, SaaidPetit, Christinedeafnessneurotransmitter releasesynaptic exocytotic machinerysynaptopathyhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Hearing relies on rapid, temporally precise, and sustained neurotransmitter release at the ribbon synapses of sensory cells, the inner hair cells (IHCs). This process requires otoferlin, a six C2-domain, Ca2+-binding transmembrane protein of synaptic vesicles. To decipher the role of otoferlin in the synaptic vesicle cycle, we produced knock-in mice (Otof Ala515,Ala517/Ala515,Ala517) with lower Ca2+-binding affinity of the C2C domain. The IHC ribbon synapse structure, synaptic Ca2+ currents, and otoferlin distribution were unaffected in these mutant mice, but auditory brainstem response wave-I amplitude was reduced. Lower Ca2+ sensitivity and delay of the fast and sustained components of synaptic exocytosis were revealed by membrane capacitance measurement upon modulations of intracellular Ca2+ concentration, by varying Ca2+ influx through voltage-gated Ca2+-channels or Ca2+ uncaging. Otoferlin thus functions as a Ca2+ sensor, setting the rates of primed vesicle fusion with the presynaptic plasma membrane and synaptic vesicle pool replenishment in the IHC active zone.Fil: Michalski, Nicolas. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; FranciaFil: Goutman, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Auclair, Sarah Marie. University of Yale; Estados UnidosFil: Boutet de Monvel, Jaques. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; FranciaFil: Tertrais, margot. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Bordeaux; FranciaFil: Emptoz, Alice. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; FranciaFil: Parrin, Alexandre. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; FranciaFil: Nouaille, Sylvie. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; FranciaFil: Guillon, Marc. Centre National de la Recherche Scientifique; Francia. University Paris Descartes; FranciaFil: Sachse, Martin. Instituto Pasteur; FranciaFil: Ciric, Danica. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; FranciaFil: Bahloul, Amel. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia. Centre National de la Recherche Scientifique; FranciaFil: Hardelin, Jean Pierre. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; FranciaFil: Sutton, Roger Bryan. Texas Tech University; Estados UnidosFil: Avan, Paul. Université Clermont Auvergne; Francia. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Krishnakumar, Shyam S.. University of Yale; Estados UnidosFil: Rothman, James E.. University of Yale; Estados Unidos. University College London; Reino UnidoFil: Dulon, Didier. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Bordeaux; FranciaFil: Safieddine, Saaid. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia. Centre National de la Recherche Scientifique; Francia. University College London; Reino UnidoFil: Petit, Christine. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia. Institut de la Vision; FranciaeLife Sciences Publications2017-11-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/70927Michalski, Nicolas; Goutman, Juan Diego; Auclair, Sarah Marie; Boutet de Monvel, Jaques; Tertrais, margot; et al.; Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses ; eLife Sciences Publications; eLife; 2017; 6; 7-11-2017; 1-34; e310132050-084XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://elifesciences.org/articles/31013info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.31013.001info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:40:04Zoai:ri.conicet.gov.ar:11336/70927instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:40:05.116CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses
title Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses
spellingShingle Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses
Michalski, Nicolas
deafness
neurotransmitter release
synaptic exocytotic machinery
synaptopathy
title_short Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses
title_full Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses
title_fullStr Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses
title_full_unstemmed Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses
title_sort Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses
dc.creator.none.fl_str_mv Michalski, Nicolas
Goutman, Juan Diego
Auclair, Sarah Marie
Boutet de Monvel, Jaques
Tertrais, margot
Emptoz, Alice
Parrin, Alexandre
Nouaille, Sylvie
Guillon, Marc
Sachse, Martin
Ciric, Danica
Bahloul, Amel
Hardelin, Jean Pierre
Sutton, Roger Bryan
Avan, Paul
Krishnakumar, Shyam S.
Rothman, James E.
Dulon, Didier
Safieddine, Saaid
Petit, Christine
author Michalski, Nicolas
author_facet Michalski, Nicolas
Goutman, Juan Diego
Auclair, Sarah Marie
Boutet de Monvel, Jaques
Tertrais, margot
Emptoz, Alice
Parrin, Alexandre
Nouaille, Sylvie
Guillon, Marc
Sachse, Martin
Ciric, Danica
Bahloul, Amel
Hardelin, Jean Pierre
Sutton, Roger Bryan
Avan, Paul
Krishnakumar, Shyam S.
Rothman, James E.
Dulon, Didier
Safieddine, Saaid
Petit, Christine
author_role author
author2 Goutman, Juan Diego
Auclair, Sarah Marie
Boutet de Monvel, Jaques
Tertrais, margot
Emptoz, Alice
Parrin, Alexandre
Nouaille, Sylvie
Guillon, Marc
Sachse, Martin
Ciric, Danica
Bahloul, Amel
Hardelin, Jean Pierre
Sutton, Roger Bryan
Avan, Paul
Krishnakumar, Shyam S.
Rothman, James E.
Dulon, Didier
Safieddine, Saaid
Petit, Christine
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv deafness
neurotransmitter release
synaptic exocytotic machinery
synaptopathy
topic deafness
neurotransmitter release
synaptic exocytotic machinery
synaptopathy
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hearing relies on rapid, temporally precise, and sustained neurotransmitter release at the ribbon synapses of sensory cells, the inner hair cells (IHCs). This process requires otoferlin, a six C2-domain, Ca2+-binding transmembrane protein of synaptic vesicles. To decipher the role of otoferlin in the synaptic vesicle cycle, we produced knock-in mice (Otof Ala515,Ala517/Ala515,Ala517) with lower Ca2+-binding affinity of the C2C domain. The IHC ribbon synapse structure, synaptic Ca2+ currents, and otoferlin distribution were unaffected in these mutant mice, but auditory brainstem response wave-I amplitude was reduced. Lower Ca2+ sensitivity and delay of the fast and sustained components of synaptic exocytosis were revealed by membrane capacitance measurement upon modulations of intracellular Ca2+ concentration, by varying Ca2+ influx through voltage-gated Ca2+-channels or Ca2+ uncaging. Otoferlin thus functions as a Ca2+ sensor, setting the rates of primed vesicle fusion with the presynaptic plasma membrane and synaptic vesicle pool replenishment in the IHC active zone.
Fil: Michalski, Nicolas. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia
Fil: Goutman, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Auclair, Sarah Marie. University of Yale; Estados Unidos
Fil: Boutet de Monvel, Jaques. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia
Fil: Tertrais, margot. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Bordeaux; Francia
Fil: Emptoz, Alice. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia
Fil: Parrin, Alexandre. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia
Fil: Nouaille, Sylvie. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia
Fil: Guillon, Marc. Centre National de la Recherche Scientifique; Francia. University Paris Descartes; Francia
Fil: Sachse, Martin. Instituto Pasteur; Francia
Fil: Ciric, Danica. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia
Fil: Bahloul, Amel. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Hardelin, Jean Pierre. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia
Fil: Sutton, Roger Bryan. Texas Tech University; Estados Unidos
Fil: Avan, Paul. Université Clermont Auvergne; Francia. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Krishnakumar, Shyam S.. University of Yale; Estados Unidos
Fil: Rothman, James E.. University of Yale; Estados Unidos. University College London; Reino Unido
Fil: Dulon, Didier. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Bordeaux; Francia
Fil: Safieddine, Saaid. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia. Centre National de la Recherche Scientifique; Francia. University College London; Reino Unido
Fil: Petit, Christine. Instituto Pasteur; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Universite de Paris VI; Francia. Institut de la Vision; Francia
description Hearing relies on rapid, temporally precise, and sustained neurotransmitter release at the ribbon synapses of sensory cells, the inner hair cells (IHCs). This process requires otoferlin, a six C2-domain, Ca2+-binding transmembrane protein of synaptic vesicles. To decipher the role of otoferlin in the synaptic vesicle cycle, we produced knock-in mice (Otof Ala515,Ala517/Ala515,Ala517) with lower Ca2+-binding affinity of the C2C domain. The IHC ribbon synapse structure, synaptic Ca2+ currents, and otoferlin distribution were unaffected in these mutant mice, but auditory brainstem response wave-I amplitude was reduced. Lower Ca2+ sensitivity and delay of the fast and sustained components of synaptic exocytosis were revealed by membrane capacitance measurement upon modulations of intracellular Ca2+ concentration, by varying Ca2+ influx through voltage-gated Ca2+-channels or Ca2+ uncaging. Otoferlin thus functions as a Ca2+ sensor, setting the rates of primed vesicle fusion with the presynaptic plasma membrane and synaptic vesicle pool replenishment in the IHC active zone.
publishDate 2017
dc.date.none.fl_str_mv 2017-11-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/70927
Michalski, Nicolas; Goutman, Juan Diego; Auclair, Sarah Marie; Boutet de Monvel, Jaques; Tertrais, margot; et al.; Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses ; eLife Sciences Publications; eLife; 2017; 6; 7-11-2017; 1-34; e31013
2050-084X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/70927
identifier_str_mv Michalski, Nicolas; Goutman, Juan Diego; Auclair, Sarah Marie; Boutet de Monvel, Jaques; Tertrais, margot; et al.; Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses ; eLife Sciences Publications; eLife; 2017; 6; 7-11-2017; 1-34; e31013
2050-084X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://elifesciences.org/articles/31013
info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.31013.001
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv eLife Sciences Publications
publisher.none.fl_str_mv eLife Sciences Publications
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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