Author response: Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming [peer_review]

Bassam Tawfik, Joana S Martins, Sébastien Houy, Cordelia Imig, Paulo S Pinheiro, Sonja M Wojcik, Nils Brose, Benjamin H Cooper, Jakob Balslev Sørensen
2021 unpublished
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 Ca 2+ -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 Ca 2+ -dependent vesicle priming and
more » ... icle 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/Ca 2+ -dependent priming as a prelude to fast and slow exocytosis triggering. Tawfik et al. eLife 2021;10:e64527.
doi:10.7554/elife.64527.sa2 fatcat:vzgik7p5ubhobnghho32m2bszi