How do the SNARE proteins and synaptotagmin divide the job of fusing a vesicle? · Grey Matter

The SNAREs supply the force: synaptobrevin on the vesicle and syntaxin and SNAP-25 on the terminal wind into a four-helix bundle that zips toward the membranes and pulls them together.

How do the SNARE proteins and synaptotagmin divide the job of fusing a vesicle?

The SNAREs supply the force: synaptobrevin on the vesicle and syntaxin and SNAP-25 on the terminal wind into a four-helix bundle that zips toward the membranes and pulls them together. Before a spike they are held half-zipped, with the vesicle primed but not fused, by helper proteins such as complexin and Munc13. Synaptotagmin supplies the timing: when calcium binds its two C2 domains, they insert into the membrane and push the half-zipped complex over the last step, opening a fusion pore. Remove the SNAREs and nothing fuses; remove synaptotagmin-1 and fusion still happens, but slowly and out of step with the spike.