Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming

eLife

Sonja M Wojcik¹  Nils Brose²  Cordelia Imig²  Benjamin H Cooper²  Jakob Balslev Sørensen²  Sébastien Houy³  Joana S Martins³  Paulo S Pinheiro³  Bassam Tawfik³ 

[1] Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal;Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany;Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark;

关键词: neurotransmitter release;    chromaffin cell;    SNARE-proteins;    synaptotagmin-7;    vesicle priming;    capacitance measurements;   

DOI  :  10.7554/eLife.64527

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown