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• W4367183532 abstract "Calcium-evoked release of neurotransmitters from synaptic vesicles (SVs) is catalysed by SNARE proteins. The predominant view is that, at rest, complete assembly of SNARE complexes is inhibited ('clamped') by synaptotagmin and complexin molecules. Calcium binding by synaptotagmins releases this fusion clamp and triggers fast SV exocytosis. However, this model has not been quantitatively tested over physiological timescales. Here we describe an experimentally constrained computational modelling framework to quantitatively assess how the molecular architecture of the fusion clamp affects SV exocytosis. Our results argue that the release-of-inhibition model can indeed account for fast calcium-activated SV fusion, and that dual binding of synaptotagmin-1 and synaptotagmin-7 to the same SNARE complex enables synergistic regulation of the kinetics and plasticity of neurotransmitter release. The developed framework provides a powerful and adaptable tool to link the molecular biochemistry of presynaptic proteins to physiological data and efficiently test the plausibility of calcium-activated neurotransmitter release models." @default.
• W4367183532 created "2023-04-28" @default.
• W4367183532 creator A5010709531 @default.
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• W4367183532 date "2023-04-27" @default.
• W4367183532 modified "2023-09-28" @default.
• W4367183532 title "The release of inhibition model reproduces kinetics and plasticity of neurotransmitter release in central synapses" @default.
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• W4367183532 doi "https://doi.org/10.21203/rs.3.rs-2700789/v1" @default.
• W4367183532 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37163032" @default.
• W4367183532 hasPublicationYear "2023" @default.
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