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SNARE interactions release calcium for fusion.

On page 195, Merz and Wickner show that when two intracellular vesicles fuse, the interaction of their SNARE proteins triggers a short-lived calcium release. The work provides the first clear connection between calcium release and the fusion cycle, and supports a model in which the pairing of SNAREs in trans coordinates the downstream signals that lead to vesicle fusion.

Previous work had hinted at a requirement for calcium signaling during vesicle fusion, but it was unclear what triggered the calcium release. In the new work, the authors isolated vacuoles from mutant yeast strains and analyzed their fusion in vitro. For calcium release to occur in this system, four different vacuolar SNARE proteins from two different membranes must interact after the priming step of the fusion cycle. Staging experiments suggest that each of these trans-SNARE interaction events triggers a short-lived calcium release.

Merz and Wickner propose that, after priming, the formation of SNARE complexes between apposed membranes during the docking step could serve as a checkpoint in the fusion cycle. Once the trans-SNARE complexes form, the resulting calcium release signifies that the priming step is over, inducing downstream calcium-dependent signals that ultimately bring about fusion. ▪