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Synergistic roles of Synaptotagmin-1 and complexin in calcium-regulated neuronal exocytosis
- Source :
- eLife, eLife, Vol 9 (2020)
- Publication Year :
- 2019
-
Abstract
- Calcium (Ca2+)-evoked release of neurotransmitters from synaptic vesicles requires mechanisms both to prevent un-initiated fusion of vesicles (clamping) and to trigger fusion following Ca2+-influx. The principal components involved in these processes are the vesicular fusion machinery (SNARE proteins) and the regulatory proteins, Synaptotagmin-1 and Complexin. Here, we use a reconstituted single-vesicle fusion assay under physiologically-relevant conditions to delineate a novel mechanism by which Synaptotagmin-1 and Complexin act synergistically to establish Ca2+-regulated fusion. We find that under each vesicle, Synaptotagmin-1 oligomers bind and clamp a limited number of ‘central’ SNARE complexes via the primary interface and introduce a kinetic delay in vesicle fusion mediated by the excess of free SNAREpins. This in turn enables Complexin to arrest the remaining free ‘peripheral’ SNAREpins to produce a stably clamped vesicle. Activation of the central SNAREpins associated with Synaptotagmin-1 by Ca2+ is sufficient to trigger rapid (
- Subjects :
- Vesicle fusion
QH301-705.5
Vesicle-Associated Membrane Protein 2
Science
Structural Biology and Molecular Biophysics
Nerve Tissue Proteins
Neurotransmission
Synaptic vesicle
Membrane Fusion
General Biochemistry, Genetics and Molecular Biology
Exocytosis
Synaptotagmin 1
Mice
Complexin
Animals
Humans
Calcium Signaling
neurotransmission
Biology (General)
calcium
General Immunology and Microbiology
Chemistry
General Neuroscience
Vesicle
vesicle fusion
E. coli
General Medicine
Cell biology
Rats
Adaptor Proteins, Vesicular Transport
Kinetics
synaptotagmin
Structural biology
Synaptotagmin I
Liposomes
Mutation
Medicine
complexin
Synaptic Vesicles
SNARE Proteins
Research Article
Subjects
Details
- ISSN :
- 2050084X
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- eLife
- Accession number :
- edsair.doi.dedup.....e4f56f1bda0e9f41c428db5fb6043b67