Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release

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 transmitt...

Descripción completa

Detalles Bibliográficos
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.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/141325
Acceso en línea:http://hdl.handle.net/11336/141325
Access Level:acceso abierto
Palabra clave:C2B DOMAIN
FUSION CLAMP
SYNAPTIC TRANSMISSION
SYNAPTOTAGMIN
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descripción
Sumario: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.

Similares en LA Referencia