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https://hdl.handle.net/10316/103874
Title: | Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming | Authors: | Tawfik, Bassam Martins, Joana S Houy, Sébastien Imig, Cordelia Pinheiro, Paulo S. Wojcik, Sonja M Brose, Nils Cooper, Benjamin H Sørensen, Jakob Balslev |
Keywords: | SNARE-proteins; capacitance measurements; chromaffin cell; mouse; neuroscience; neurotransmitter release; synaptotagmin-7; vesicle priming | Issue Date: | 22-Mar-2021 | Publisher: | eLife Sciences Publications | Project: | University of Copenhagen KU2016 Novo Nordisk Foundation NNF19OC0058298 Lundbeckfonden R221-2016-1202 Independent Research Fund Denmark 0134-00141A Lundbeckfonden R34-A3740 |
Serial title, monograph or event: | eLife | Volume: | 10 | Abstract: | Synaptotagmins confer calcium-dependence to the exocytosis of secretory vesicles, but how coexpressed synaptotagmins interact remains unclear. We find that synaptotagmin-1 and synaptotagmin-7 when present alone act as standalone fast and slow Ca2+-sensors for vesicle fusion in mouse chromaffin cells. When present together, synaptotagmin-1 and synaptotagmin-7 are found in largely non-overlapping clusters on dense-core vesicles. Synaptotagmin-7 stimulates Ca2+-dependent vesicle priming and inhibits depriming, and it promotes ubMunc13-2- and phorbolester-dependent priming, especially at low resting calcium concentrations. The priming effect of synaptotagmin-7 increases the number of vesicles fusing via synaptotagmin-1, while negatively affecting their fusion speed, indicating both synergistic and competitive interactions between synaptotagmins. Synaptotagmin-7 places vesicles in close membrane apposition (<6 nm); without it, vesicles accumulate out of reach of the fusion complex (20-40 nm). We suggest that a synaptotagmin-7-dependent movement toward the membrane is involved in Munc13-2/phorbolester/Ca2+-dependent priming as a prelude to fast and slow exocytosis triggering. | URI: | https://hdl.handle.net/10316/103874 | ISSN: | 2050-084X | DOI: | 10.7554/eLife.64527 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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elife-64527-v2.pdf | 4.84 MB | Adobe PDF | View/Open |
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