Utilize este identificador para referenciar este registo: https://hdl.handle.net/10316/103874
Título: Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming
Autor: Tawfik, Bassam
Martins, Joana S
Houy, Sébastien
Imig, Cordelia
Pinheiro, Paulo S. 
Wojcik, Sonja M
Brose, Nils
Cooper, Benjamin H
Sørensen, Jakob Balslev
Palavras-chave: SNARE-proteins; capacitance measurements; chromaffin cell; mouse; neuroscience; neurotransmitter release; synaptotagmin-7; vesicle priming
Data: 22-Mar-2021
Editora: eLife Sciences Publications
Projeto: University of Copenhagen KU2016 
Novo Nordisk Foundation NNF19OC0058298 
Lundbeckfonden R221-2016-1202 
Independent Research Fund Denmark 0134-00141A 
Lundbeckfonden R34-A3740 
Título da revista, periódico, livro ou evento: eLife
Volume: 10
Resumo: 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
Direitos: openAccess
Aparece nas coleções:I&D CNC - Artigos em Revistas Internacionais

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