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dc.contributor.author
Bello, Oscar Daniel
dc.contributor.author
Jouannot, Ouardane
dc.contributor.author
Chaudhuri, Arunima
dc.contributor.author
Stroeva, Ekaterina
dc.contributor.author
Coleman, Jeff
dc.contributor.author
Volynski, Kirill E.
dc.contributor.author
Rothman, James E.
dc.contributor.author
Krishnakumar, Shyam S.
dc.date.available
2022-06-21T19:53:47Z
dc.date.issued
2018-08
dc.identifier.citation
Bello, Oscar Daniel; Jouannot, Ouardane; Chaudhuri, Arunima; Stroeva, Ekaterina; Coleman, Jeff; et al.; Synaptotagmin oligomerization is essential for calcium control of regulated exocytosis; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 115; 32; 8-2018; 7624-7631
dc.identifier.issn
0027-8424
dc.identifier.uri
http://hdl.handle.net/11336/160123
dc.description.abstract
Regulated exocytosis, which underlies many intercellular signaling events, is a tightly controlled process often triggered by calcium ion(s) (Ca2+). Despite considerable insight into the central components involved, namely, the core fusion machinery [soluble N-ethylmaleimide?sensitive factor attachment protein receptor (SNARE)] and the principal Ca2+ sensor [C2-domain proteins like synaptotagmin (Syt)], the molecular mechanism of Ca2+-dependent release has been unclear. Here, we report that the Ca2+-sensitive oligomers of Syt1, a conserved structural feature among several C2-domain proteins, play a critical role in orchestrating Ca2+-coupled vesicular release. This follows from pHluorin-based imaging of single-vesicle exocytosis in pheochromocytoma (PC12) cells showing that selective disruption of Syt1 oligomerization using a structure-directed mutation (F349A) dramatically increases the normally low levels of constitutive exocytosis to effectively occlude Ca2+-stimulated release. We propose a parsimonious model whereby Ca2+-sensitive oligomers of Syt (or a similar C2-domain protein) assembled at the site of docking physically block spontaneous fusion until disrupted by Ca2+. Our data further suggest Ca2+-coupled vesicular release is triggered by removal of the inhibition, rather than by direct activation of the fusion machinery.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
National Academy of Sciences
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CALCIUM
dc.subject
PC12 CELLS
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REGULATED EXOCYTOSIS
dc.subject
SNARE PROTEIN
dc.subject
SYNAPTOTAGMIN
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Synaptotagmin oligomerization is essential for calcium control of regulated exocytosis
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-06-16T14:06:32Z
dc.journal.volume
115
dc.journal.number
32
dc.journal.pagination
7624-7631
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Bello, Oscar Daniel. University of Yale. School of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mendoza. Instituto de Histologia y Embriologia de Mendoza Dr. Mario H. Burgos. Grupo Vinculado de Investigacion y Desarrollo Biotecnologico Aplicado Al Diagnostico Al Ihem | Universidad Nacional de Cuyo. Facultad de Ciencias Medicas. Instituto de Histologia y Embriologia de Mendoza Dr. Mario H. Burgos. Grupo Vinculado de Investigacion y Desarrollo Biotecnologico Aplicado Al Diagnostico Al Ihem.; Argentina. University College London; Estados Unidos
dc.description.fil
Fil: Jouannot, Ouardane. University of Yale. School of Medicine; Estados Unidos
dc.description.fil
Fil: Chaudhuri, Arunima. University of Yale. School of Medicine; Estados Unidos
dc.description.fil
Fil: Stroeva, Ekaterina. University of Yale. School of Medicine; Estados Unidos
dc.description.fil
Fil: Coleman, Jeff. University of Yale. School of Medicine; Estados Unidos
dc.description.fil
Fil: Volynski, Kirill E.. University College London; Reino Unido
dc.description.fil
Fil: Rothman, James E.. University of Yale. School of Medicine; Estados Unidos. University College London; Estados Unidos
dc.description.fil
Fil: Krishnakumar, Shyam S.. University of Yale. School of Medicine; Estados Unidos. University College London; Estados Unidos
dc.journal.title
Proceedings of the National Academy of Sciences of The United States of America
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1073/pnas.1808792115
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/doi/pdf/10.1073/pnas.1808792115
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