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Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release
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Tagliatti, Erica, Bello, Oscar D., Mendonça, Philipe R. F., Kotzadimitriou, Dimitrios, Nicholson, Elizabeth, Coleman, Jeff, Timofeeva, Yulia, Rothman, James E., Krishnakumar, Shyam S. and Volynski, Kirill E. (2020) Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release. Proceedings of the National Academy of Sciences, 117 (7). pp. 3819-3827. doi:10.1073/pnas.1920403117
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WRAP-Synaptotagmin-1-oligomers-clamp-regulate-different-modes-neurotransmitter-release-Timofeeva-2020.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution Non-commercial No Derivatives 4.0. Download (1884Kb) | Preview |
Official URL: http://dx.doi.org/10.1073/pnas.1920403117
Abstract
Release of neurotransmitters relies on submillisecond coupling of synaptic vesicle fusion to the triggering signal: AP-evoked presynaptic Ca2+ influx. The key player that controls exocytosis of the synaptic vesicle is the Ca2+ sensor synaptotagmin 1 (Syt1). While the Ca2+ activation of Syt1 has been extensively characterized, how Syt1 reversibly clamps vesicular fusion remains enigmatic. Here, using a targeted mutation combined with fluorescence imaging and electrophysiology, we show that the structural feature of Syt1 to self-oligomerize provides the molecular basis for clamping of spontaneous and asynchronous release but is not required for triggering of synchronous release. Our findings propose a mechanistic model that explains how Syt1 oligomers regulate different modes of transmitter release in neuronal synapses.
| Item Type: | Journal Article | |||||||||
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| Subjects: | Q Science > QP Physiology | |||||||||
| Divisions: | Faculty of Science > Centre for Complexity Science Faculty of Science > Computer Science |
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| Library of Congress Subject Headings (LCSH): | Neural transmission -- Regulation, Neurotransmitters, Synaptic vesicles, Synaptotagmin-1 | |||||||||
| Journal or Publication Title: | Proceedings of the National Academy of Sciences | |||||||||
| Publisher: | National Academy of Sciences | |||||||||
| ISSN: | 0027-8424 | |||||||||
| Official Date: | 18 February 2020 | |||||||||
| Dates: |
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| Volume: | 117 | |||||||||
| Number: | 7 | |||||||||
| Page Range: | pp. 3819-3827 | |||||||||
| DOI: | 10.1073/pnas.1920403117 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Open Access | |||||||||
| RIOXX Funder/Project Grant: |
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