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dc.contributor.author
Tagliatti, Erica
dc.contributor.author
Bello, Oscar Daniel
dc.contributor.author
Mendonça, Philipe R. F.
dc.contributor.author
Kotzadimitriou, Dimitrios
dc.contributor.author
Nicholson, Elizabeth
dc.contributor.author
Coleman, Jeff
dc.contributor.author
Timofeeva, Yulia
dc.contributor.author
Rothman, James E.
dc.contributor.author
Krishnakumar, Shyam S.
dc.contributor.author
Volynski, Kirill E.
dc.date.available
2021-09-23T13:27:56Z
dc.date.issued
2020-02
dc.identifier.citation
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
dc.identifier.issn
0027-8424
dc.identifier.uri
http://hdl.handle.net/11336/141325
dc.description.abstract
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.
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
C2B DOMAIN
dc.subject
FUSION CLAMP
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SYNAPTIC TRANSMISSION
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SYNAPTOTAGMIN
dc.subject.classification
Biofísica
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2021-09-06T19:55:04Z
dc.journal.volume
117
dc.journal.number
7
dc.journal.pagination
3819-3827
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Tagliatti, Erica. University College London; Estados Unidos
dc.description.fil
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
dc.description.fil
Fil: Mendonça, Philipe R. F.. University College London; Estados Unidos
dc.description.fil
Fil: Kotzadimitriou, Dimitrios. University College London; Estados Unidos
dc.description.fil
Fil: Nicholson, Elizabeth. University College London; Estados Unidos
dc.description.fil
Fil: Coleman, Jeff. University of Yale. School of Medicine; Estados Unidos
dc.description.fil
Fil: Timofeeva, Yulia. University College London; Estados Unidos
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.description.fil
Fil: Volynski, Kirill E.. 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/url/http://www.pnas.org/lookup/doi/10.1073/pnas.1920403117
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1073/pnas.1920403117
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