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The release of inhibition model reproduces kinetics and plasticity of neurotransmitter release in central synapses
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Norman, Christopher A., Krishnakumar, Shyam S., Timofeeva, Yulia and Volynski, Kirill E. (2023) The release of inhibition model reproduces kinetics and plasticity of neurotransmitter release in central synapses. Communications Biology, 6 (1). 1091. doi:10.1038/s42003-023-05445-2 ISSN 2399-3642.
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Official URL: http://dx.doi.org/10.1038/s42003-023-05445-2
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.
Item Type: | Journal Article | ||||||
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Subjects: | Q Science > QA Mathematics Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Computer Science Faculty of Science, Engineering and Medicine > Science > Mathematics |
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Library of Congress Subject Headings (LCSH): | Neurotransmitters, Synaptic vesicles, Synapses, Calcium | ||||||
Journal or Publication Title: | Communications Biology | ||||||
Publisher: | Nature Publishing Group | ||||||
ISSN: | 2399-3642 | ||||||
Official Date: | 27 October 2023 | ||||||
Dates: |
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Volume: | 6 | ||||||
Number: | 1 | ||||||
Article Number: | 1091 | ||||||
DOI: | 10.1038/s42003-023-05445-2 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||
Date of first compliant deposit: | 27 October 2023 | ||||||
Date of first compliant Open Access: | 27 October 2023 |
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