Calcium sensitive ring-like oligomers formed by synaptotagmin

Autores
Wang, Jing; Bello, Oscar Daniel; Auclair, Sarah M.; Coleman, Jeff; Pincet, Frederic; Krishnakumar, Shyam S.; Sindelar, Charles V.; Rothman, James E.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The synaptic vesicle protein synaptotagmin-1 (SYT) is required to couple calcium influx to the membrane fusion machinery. However, the structural mechanism underlying this process is unclear. Here we report an unexpected circular arrangement (ring) of SYT's cytosolic domain (C2AB) formed on lipid monolayers in the absence of free calcium ions as revealed by electron microscopy. Rings vary in diameter from 18-43 nm, corresponding to 11-26 molecules of SYT. Continuous stacking of the SYT rings occasionally converts both lipid monolayers and bilayers into protein-coated tubes. Helical reconstruction of the SYT tubes shows that one of the C2 domains (most likely C2B, based on its biochemical properties) interacts with the membrane and is involved in ring formation, and the other C2 domain points radially outward. SYT rings are disrupted rapidly by physiological concentrations of free calcium but not by magnesium. Assuming that calcium-free SYT rings are physiologically relevant, these results suggest a simple and novel mechanism by which SYT regulates neurotransmitter release: The ring acts as a spacer to prevent the completion of the soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE) complex assembly, thereby clamping fusion in the absence of calcium. When the ring disassembles in the presence of calcium, fusion proceeds unimpeded.
Fil: Wang, Jing. University of Yale. School of Medicine; Estados Unidos
Fil: Bello, Oscar Daniel. University of Yale. School of Medicine; Estados Unidos. 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
Fil: Auclair, Sarah M.. University of Yale. School of Medicine; Estados Unidos
Fil: Coleman, Jeff. University of Yale. School of Medicine; Estados Unidos
Fil: Pincet, Frederic. University of Yale. School of Medicine; Estados Unidos. Ecole Normale Supérieure; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Krishnakumar, Shyam S.. University of Yale. School of Medicine; Estados Unidos
Fil: Sindelar, Charles V.. University of Yale. School of Medicine; Estados Unidos
Fil: Rothman, James E.. University of Yale. School of Medicine; Estados Unidos
Materia
SYNAPTOTAGMIN
MEMBRANE FUSION
SNARES
NEUROTRANSMITTER RELEASE
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:11336/182837
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/182837
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Calcium sensitive ring-like oligomers formed by synaptotagminWang, JingBello, Oscar DanielAuclair, Sarah M.Coleman, JeffPincet, FredericKrishnakumar, Shyam S.Sindelar, Charles V.Rothman, James E.SYNAPTOTAGMINMEMBRANE FUSIONSNARESNEUROTRANSMITTER RELEASEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The synaptic vesicle protein synaptotagmin-1 (SYT) is required to couple calcium influx to the membrane fusion machinery. However, the structural mechanism underlying this process is unclear. Here we report an unexpected circular arrangement (ring) of SYT's cytosolic domain (C2AB) formed on lipid monolayers in the absence of free calcium ions as revealed by electron microscopy. Rings vary in diameter from 18-43 nm, corresponding to 11-26 molecules of SYT. Continuous stacking of the SYT rings occasionally converts both lipid monolayers and bilayers into protein-coated tubes. Helical reconstruction of the SYT tubes shows that one of the C2 domains (most likely C2B, based on its biochemical properties) interacts with the membrane and is involved in ring formation, and the other C2 domain points radially outward. SYT rings are disrupted rapidly by physiological concentrations of free calcium but not by magnesium. Assuming that calcium-free SYT rings are physiologically relevant, these results suggest a simple and novel mechanism by which SYT regulates neurotransmitter release: The ring acts as a spacer to prevent the completion of the soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE) complex assembly, thereby clamping fusion in the absence of calcium. When the ring disassembles in the presence of calcium, fusion proceeds unimpeded.Fil: Wang, Jing. University of Yale. School of Medicine; Estados UnidosFil: Bello, Oscar Daniel. University of Yale. School of Medicine; Estados Unidos. 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; ArgentinaFil: Auclair, Sarah M.. University of Yale. School of Medicine; Estados UnidosFil: Coleman, Jeff. University of Yale. School of Medicine; Estados UnidosFil: Pincet, Frederic. University of Yale. School of Medicine; Estados Unidos. Ecole Normale Supérieure; Francia. Centre National de la Recherche Scientifique; FranciaFil: Krishnakumar, Shyam S.. University of Yale. School of Medicine; Estados UnidosFil: Sindelar, Charles V.. University of Yale. School of Medicine; Estados UnidosFil: Rothman, James E.. University of Yale. School of Medicine; Estados UnidosNational Academy of Sciences2014-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/182837Wang, Jing; Bello, Oscar Daniel; Auclair, Sarah M.; Coleman, Jeff; Pincet, Frederic; et al.; Calcium sensitive ring-like oligomers formed by synaptotagmin; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 111; 38; 9-2014; 13966-139710027-84241091-6490CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/cgi/doi/10.1073/pnas.1415849111info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1415849111info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:48:20Zoai:ri.conicet.gov.ar:11336/182837instacron: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 09:48:21.158CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Calcium sensitive ring-like oligomers formed by synaptotagmin
title Calcium sensitive ring-like oligomers formed by synaptotagmin
spellingShingle Calcium sensitive ring-like oligomers formed by synaptotagmin
Wang, Jing
SYNAPTOTAGMIN
MEMBRANE FUSION
SNARES
NEUROTRANSMITTER RELEASE
title_short Calcium sensitive ring-like oligomers formed by synaptotagmin
title_full Calcium sensitive ring-like oligomers formed by synaptotagmin
title_fullStr Calcium sensitive ring-like oligomers formed by synaptotagmin
title_full_unstemmed Calcium sensitive ring-like oligomers formed by synaptotagmin
title_sort Calcium sensitive ring-like oligomers formed by synaptotagmin
dc.creator.none.fl_str_mv Wang, Jing
Bello, Oscar Daniel
Auclair, Sarah M.
Coleman, Jeff
Pincet, Frederic
Krishnakumar, Shyam S.
Sindelar, Charles V.
Rothman, James E.
author Wang, Jing
author_facet Wang, Jing
Bello, Oscar Daniel
Auclair, Sarah M.
Coleman, Jeff
Pincet, Frederic
Krishnakumar, Shyam S.
Sindelar, Charles V.
Rothman, James E.
author_role author
author2 Bello, Oscar Daniel
Auclair, Sarah M.
Coleman, Jeff
Pincet, Frederic
Krishnakumar, Shyam S.
Sindelar, Charles V.
Rothman, James E.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv SYNAPTOTAGMIN
MEMBRANE FUSION
SNARES
NEUROTRANSMITTER RELEASE
topic SYNAPTOTAGMIN
MEMBRANE FUSION
SNARES
NEUROTRANSMITTER RELEASE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The synaptic vesicle protein synaptotagmin-1 (SYT) is required to couple calcium influx to the membrane fusion machinery. However, the structural mechanism underlying this process is unclear. Here we report an unexpected circular arrangement (ring) of SYT's cytosolic domain (C2AB) formed on lipid monolayers in the absence of free calcium ions as revealed by electron microscopy. Rings vary in diameter from 18-43 nm, corresponding to 11-26 molecules of SYT. Continuous stacking of the SYT rings occasionally converts both lipid monolayers and bilayers into protein-coated tubes. Helical reconstruction of the SYT tubes shows that one of the C2 domains (most likely C2B, based on its biochemical properties) interacts with the membrane and is involved in ring formation, and the other C2 domain points radially outward. SYT rings are disrupted rapidly by physiological concentrations of free calcium but not by magnesium. Assuming that calcium-free SYT rings are physiologically relevant, these results suggest a simple and novel mechanism by which SYT regulates neurotransmitter release: The ring acts as a spacer to prevent the completion of the soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE) complex assembly, thereby clamping fusion in the absence of calcium. When the ring disassembles in the presence of calcium, fusion proceeds unimpeded.
Fil: Wang, Jing. University of Yale. School of Medicine; Estados Unidos
Fil: Bello, Oscar Daniel. University of Yale. School of Medicine; Estados Unidos. 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
Fil: Auclair, Sarah M.. University of Yale. School of Medicine; Estados Unidos
Fil: Coleman, Jeff. University of Yale. School of Medicine; Estados Unidos
Fil: Pincet, Frederic. University of Yale. School of Medicine; Estados Unidos. Ecole Normale Supérieure; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Krishnakumar, Shyam S.. University of Yale. School of Medicine; Estados Unidos
Fil: Sindelar, Charles V.. University of Yale. School of Medicine; Estados Unidos
Fil: Rothman, James E.. University of Yale. School of Medicine; Estados Unidos
description The synaptic vesicle protein synaptotagmin-1 (SYT) is required to couple calcium influx to the membrane fusion machinery. However, the structural mechanism underlying this process is unclear. Here we report an unexpected circular arrangement (ring) of SYT's cytosolic domain (C2AB) formed on lipid monolayers in the absence of free calcium ions as revealed by electron microscopy. Rings vary in diameter from 18-43 nm, corresponding to 11-26 molecules of SYT. Continuous stacking of the SYT rings occasionally converts both lipid monolayers and bilayers into protein-coated tubes. Helical reconstruction of the SYT tubes shows that one of the C2 domains (most likely C2B, based on its biochemical properties) interacts with the membrane and is involved in ring formation, and the other C2 domain points radially outward. SYT rings are disrupted rapidly by physiological concentrations of free calcium but not by magnesium. Assuming that calcium-free SYT rings are physiologically relevant, these results suggest a simple and novel mechanism by which SYT regulates neurotransmitter release: The ring acts as a spacer to prevent the completion of the soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE) complex assembly, thereby clamping fusion in the absence of calcium. When the ring disassembles in the presence of calcium, fusion proceeds unimpeded.
publishDate 2014
dc.date.none.fl_str_mv 2014-09
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/11336/182837
Wang, Jing; Bello, Oscar Daniel; Auclair, Sarah M.; Coleman, Jeff; Pincet, Frederic; et al.; Calcium sensitive ring-like oligomers formed by synaptotagmin; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 111; 38; 9-2014; 13966-13971
0027-8424
1091-6490
CONICET Digital
CONICET
url http://hdl.handle.net/11336/182837
identifier_str_mv Wang, Jing; Bello, Oscar Daniel; Auclair, Sarah M.; Coleman, Jeff; Pincet, Frederic; et al.; Calcium sensitive ring-like oligomers formed by synaptotagmin; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 111; 38; 9-2014; 13966-13971
0027-8424
1091-6490
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/cgi/doi/10.1073/pnas.1415849111
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1415849111
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_ 1842268919369302016
score 13.13397

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