The same membrane rearrangements that prompt two cargo-carrying vesicles to unite can also provoke them to burst. Vincent Starari, Youngsoo Jun, and William Wickner (Dartmouth Medical School, Hanover, NH) explain how cells favor fusion over breakage.

Fusion between, say, the Golgi apparatus and a vesicle fresh from the ER requires a crew of molecules. The participants include Rab GTPases, Rab effectors that bind active Rab and transmit its signals, and SNARE proteins, which interlock to draw the opposing membranes together. Liposomes carrying SNAREs fuse in vitro, but recent studies revealed that many liposomes rupture, which doesn't happen in cells.

To investigate the cause of lysis, the authors observed purified yeast vacuoles, which merged without bursting. They then tracked vacuoles from yeast engineered to overexpress four SNARE proteins. Although some of the containers fused, up to 80% of them popped. “That's not like a little leak...

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