Autor(es):
Tawfik, Bassam ; Martins, Joana S ; Houy, Sébastien ; Imig, Cordelia ; Pinheiro, Paulo S. ; Wojcik, Sonja M ; Brose, Nils ; Cooper, Benjamin H ; Sørensen, Jakob Balslev
Data: 2021
Identificador Persistente: https://hdl.handle.net/10316/103874
Origem: Estudo Geral - Universidade de Coimbra
Assunto(s): SNARE-proteins; capacitance measurements; chromaffin cell; mouse; neuroscience; neurotransmitter release; synaptotagmin-7; vesicle priming; Animals; Calcium; Cell Membrane; Chromaffin Cells; Electron Microscope Tomography; Exocytosis; Intracellular Signaling Peptides and Proteins; Membrane Fusion; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Secretory Vesicles; Synaptotagmins
Descrição
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.
