SNAREs contribute to the specificity of membrane fusion

Intracellular membrane fusion is mediated by the formation of a four-helix bundle comprised of SNARE proteins. Every cell expresses a large number of SNARE proteins that are localized to particular membrane compartments, sugg esting that the fidelity of vesicle trafficking might in part be determined by specific SNARE pairing. However, the promiscuity of SNARE pairing in vi tro suggests that the information for membrane compartment organization is not encoded in the inherent ability of SNAREs to form complexes. Here, we s how that exocytosis of norepinephrine from PC12 cells is only inhibited or rescued by specific SNAREs. The data suggest that SNARE pairing does underl ie vesicle trafficking fidelity, and that specific SNARE interactions with other proteins may facilitate the correct pairing.