Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release

Autores
Tagliatti, Erica; Bello, Oscar Daniel; Mendonça, Philipe R. F.; Kotzadimitriou, Dimitrios; Nicholson, Elizabeth; Coleman, Jeff; Timofeeva, Yulia; Rothman, James E.; Krishnakumar, Shyam S.; Volynski, Kirill E.
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Synaptotagmin 1 (Syt1) synchronizes neurotransmitter release to action potentials (APs) acting as the fast Ca2+ release sensor and as the inhibitor (clamp) of spontaneous and delayed asynchronous release. While the Syt1 Ca2+ activation mechanism has been well-characterized, how Syt1 clamps transmitter release remains enigmatic. Here we show that C2B domain-dependent oligomerization provides the molecular basis for the Syt1 clamping function. This follows from the investigation of a designed mutation (F349A), which selectively destabilizes Syt1 oligomerization. Using a combination of fluorescence imaging and electrophysiology in neocortical synapses, we show that Syt1F349A is more efficient than wild-type Syt1 (Syt1WT) in triggering synchronous transmitter release but fails to clamp spontaneous and synaptotagmin 7 (Syt7)-mediated asynchronous release components both in rescue (Syt1−/− knockout background) and dominant-interference (Syt1+/+ background) conditions. Thus, we conclude that Ca2+-sensitive Syt1 oligomers, acting as an exocytosis clamp, are critical for maintaining the balance among the different modes of neurotransmitter release.
Fil: Tagliatti, Erica. University College London; Estados Unidos
Fil: Bello, Oscar Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. University College London; Estados Unidos
Fil: Mendonça, Philipe R. F.. University College London; Estados Unidos
Fil: Kotzadimitriou, Dimitrios. University College London; Estados Unidos
Fil: Nicholson, Elizabeth. University College London; Estados Unidos
Fil: Coleman, Jeff. University of Yale. School of Medicine; Estados Unidos
Fil: Timofeeva, Yulia. University College London; Estados Unidos
Fil: Rothman, James E.. University of Yale. School of Medicine; Estados Unidos. University College London; Estados Unidos
Fil: Krishnakumar, Shyam S.. University of Yale. School of Medicine; Estados Unidos. University College London; Estados Unidos
Fil: Volynski, Kirill E.. University of Yale. School of Medicine; Estados Unidos. University College London; Estados Unidos
Materia
C2B DOMAIN
FUSION CLAMP
SYNAPTIC TRANSMISSION
SYNAPTOTAGMIN
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:11336/141325
Acceder
id CONICETDig_e7882f319dd4cc41d92b3ac18acefe4e
oai_identifier_str oai:ri.conicet.gov.ar:11336/141325
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter releaseTagliatti, EricaBello, Oscar DanielMendonça, Philipe R. F.Kotzadimitriou, DimitriosNicholson, ElizabethColeman, JeffTimofeeva, YuliaRothman, James E.Krishnakumar, Shyam S.Volynski, Kirill E.C2B DOMAINFUSION CLAMPSYNAPTIC TRANSMISSIONSYNAPTOTAGMINhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Synaptotagmin 1 (Syt1) synchronizes neurotransmitter release to action potentials (APs) acting as the fast Ca2+ release sensor and as the inhibitor (clamp) of spontaneous and delayed asynchronous release. While the Syt1 Ca2+ activation mechanism has been well-characterized, how Syt1 clamps transmitter release remains enigmatic. Here we show that C2B domain-dependent oligomerization provides the molecular basis for the Syt1 clamping function. This follows from the investigation of a designed mutation (F349A), which selectively destabilizes Syt1 oligomerization. Using a combination of fluorescence imaging and electrophysiology in neocortical synapses, we show that Syt1F349A is more efficient than wild-type Syt1 (Syt1WT) in triggering synchronous transmitter release but fails to clamp spontaneous and synaptotagmin 7 (Syt7)-mediated asynchronous release components both in rescue (Syt1−/− knockout background) and dominant-interference (Syt1+/+ background) conditions. Thus, we conclude that Ca2+-sensitive Syt1 oligomers, acting as an exocytosis clamp, are critical for maintaining the balance among the different modes of neurotransmitter release.Fil: Tagliatti, Erica. University College London; Estados UnidosFil: Bello, Oscar Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. University College London; Estados UnidosFil: Mendonça, Philipe R. F.. University College London; Estados UnidosFil: Kotzadimitriou, Dimitrios. University College London; Estados UnidosFil: Nicholson, Elizabeth. University College London; Estados UnidosFil: Coleman, Jeff. University of Yale. School of Medicine; Estados UnidosFil: Timofeeva, Yulia. University College London; Estados UnidosFil: Rothman, James E.. University of Yale. School of Medicine; Estados Unidos. University College London; Estados UnidosFil: Krishnakumar, Shyam S.. University of Yale. School of Medicine; Estados Unidos. University College London; Estados UnidosFil: Volynski, Kirill E.. University of Yale. School of Medicine; Estados Unidos. University College London; Estados UnidosNational Academy of Sciences2020-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/141325Tagliatti, Erica; Bello, Oscar Daniel; Mendonça, Philipe R. F.; Kotzadimitriou, Dimitrios; Nicholson, Elizabeth; et al.; Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 117; 7; 2-2020; 3819-38270027-8424CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/lookup/doi/10.1073/pnas.1920403117info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1920403117info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:10:16Zoai:ri.conicet.gov.ar:11336/141325instacron: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:34982025-09-03 10:10:16.839CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release
title Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release
spellingShingle Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release
Tagliatti, Erica
C2B DOMAIN
FUSION CLAMP
SYNAPTIC TRANSMISSION
SYNAPTOTAGMIN
title_short Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release
title_full Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release
title_fullStr Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release
title_full_unstemmed Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release
title_sort Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release
dc.creator.none.fl_str_mv Tagliatti, Erica
Bello, Oscar Daniel
Mendonça, Philipe R. F.
Kotzadimitriou, Dimitrios
Nicholson, Elizabeth
Coleman, Jeff
Timofeeva, Yulia
Rothman, James E.
Krishnakumar, Shyam S.
Volynski, Kirill E.
author Tagliatti, Erica
author_facet Tagliatti, Erica
Bello, Oscar Daniel
Mendonça, Philipe R. F.
Kotzadimitriou, Dimitrios
Nicholson, Elizabeth
Coleman, Jeff
Timofeeva, Yulia
Rothman, James E.
Krishnakumar, Shyam S.
Volynski, Kirill E.
author_role author
author2 Bello, Oscar Daniel
Mendonça, Philipe R. F.
Kotzadimitriou, Dimitrios
Nicholson, Elizabeth
Coleman, Jeff
Timofeeva, Yulia
Rothman, James E.
Krishnakumar, Shyam S.
Volynski, Kirill E.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv C2B DOMAIN
FUSION CLAMP
SYNAPTIC TRANSMISSION
SYNAPTOTAGMIN
topic C2B DOMAIN
FUSION CLAMP
SYNAPTIC TRANSMISSION
SYNAPTOTAGMIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Synaptotagmin 1 (Syt1) synchronizes neurotransmitter release to action potentials (APs) acting as the fast Ca2+ release sensor and as the inhibitor (clamp) of spontaneous and delayed asynchronous release. While the Syt1 Ca2+ activation mechanism has been well-characterized, how Syt1 clamps transmitter release remains enigmatic. Here we show that C2B domain-dependent oligomerization provides the molecular basis for the Syt1 clamping function. This follows from the investigation of a designed mutation (F349A), which selectively destabilizes Syt1 oligomerization. Using a combination of fluorescence imaging and electrophysiology in neocortical synapses, we show that Syt1F349A is more efficient than wild-type Syt1 (Syt1WT) in triggering synchronous transmitter release but fails to clamp spontaneous and synaptotagmin 7 (Syt7)-mediated asynchronous release components both in rescue (Syt1−/− knockout background) and dominant-interference (Syt1+/+ background) conditions. Thus, we conclude that Ca2+-sensitive Syt1 oligomers, acting as an exocytosis clamp, are critical for maintaining the balance among the different modes of neurotransmitter release.
Fil: Tagliatti, Erica. University College London; Estados Unidos
Fil: Bello, Oscar Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. University College London; Estados Unidos
Fil: Mendonça, Philipe R. F.. University College London; Estados Unidos
Fil: Kotzadimitriou, Dimitrios. University College London; Estados Unidos
Fil: Nicholson, Elizabeth. University College London; Estados Unidos
Fil: Coleman, Jeff. University of Yale. School of Medicine; Estados Unidos
Fil: Timofeeva, Yulia. University College London; Estados Unidos
Fil: Rothman, James E.. University of Yale. School of Medicine; Estados Unidos. University College London; Estados Unidos
Fil: Krishnakumar, Shyam S.. University of Yale. School of Medicine; Estados Unidos. University College London; Estados Unidos
Fil: Volynski, Kirill E.. University of Yale. School of Medicine; Estados Unidos. University College London; Estados Unidos
description Synaptotagmin 1 (Syt1) synchronizes neurotransmitter release to action potentials (APs) acting as the fast Ca2+ release sensor and as the inhibitor (clamp) of spontaneous and delayed asynchronous release. While the Syt1 Ca2+ activation mechanism has been well-characterized, how Syt1 clamps transmitter release remains enigmatic. Here we show that C2B domain-dependent oligomerization provides the molecular basis for the Syt1 clamping function. This follows from the investigation of a designed mutation (F349A), which selectively destabilizes Syt1 oligomerization. Using a combination of fluorescence imaging and electrophysiology in neocortical synapses, we show that Syt1F349A is more efficient than wild-type Syt1 (Syt1WT) in triggering synchronous transmitter release but fails to clamp spontaneous and synaptotagmin 7 (Syt7)-mediated asynchronous release components both in rescue (Syt1−/− knockout background) and dominant-interference (Syt1+/+ background) conditions. Thus, we conclude that Ca2+-sensitive Syt1 oligomers, acting as an exocytosis clamp, are critical for maintaining the balance among the different modes of neurotransmitter release.
publishDate 2020
dc.date.none.fl_str_mv 2020-02
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/11336/141325
Tagliatti, Erica; Bello, Oscar Daniel; Mendonça, Philipe R. F.; Kotzadimitriou, Dimitrios; Nicholson, Elizabeth; et al.; Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 117; 7; 2-2020; 3819-3827
0027-8424
CONICET Digital
CONICET
url http://hdl.handle.net/11336/141325
identifier_str_mv Tagliatti, Erica; Bello, Oscar Daniel; Mendonça, Philipe R. F.; Kotzadimitriou, Dimitrios; Nicholson, Elizabeth; et al.; Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 117; 7; 2-2020; 3819-3827
0027-8424
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/lookup/doi/10.1073/pnas.1920403117
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1920403117
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 National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
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_ 1842270111955681280
score 13.13397

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