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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/70927
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T10:42:06Zoai: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:34982025-09-29 10:42:06.389CONICET 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 |
_version_ |
1844614453537013760 |
score |
13.070432 |