title: SNAREs contribute to the specificity of membrane fusion.
abstract: 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, suggesting that the fidelity of vesicle trafficking might in part be determined by specific SNARE pairing. However, the promiscuity of SNARE pairing in vitro suggests that the information for membrane compartment organization is not encoded in the inherent ability of SNAREs to form complexes. Here, we show that exocytosis of norepinephrine from PC12 cells is only inhibited or rescued by specific SNAREs. The data suggest that SNARE pairing does underlie vesicle trafficking fidelity, and that specific SNARE interactions with other proteins may facilitate the correct pairing.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, California 94305, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Scales
authors.forename: Y A
authors.initials: YA
authors.lastname: Chen
authors.forename: B Y
authors.initials: BY
authors.lastname: Yoo
authors.forename: S M
authors.initials: SM
authors.lastname: Patel
authors.forename: Y C
authors.initials: YC
authors.lastname: Doung
authors.forename: R H
authors.initials: RH
authors.lastname: Scheller
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D008561:Membrane Fusion / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism; D016716:PC12 Cells / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D051381:Rats; D050600:SNARE Proteins; D012995:Solubility; D013379:Substrate Specificity; D050825:Synaptosomal-Associated Protein 25; D033921:Vesicular Transport Proteins
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D050600:SNARE Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D033921:Vesicular Transport Proteins; D001905:Botulinum Toxins; C096326:botulinum toxin type E; D009638:Norepinephrine