title: Nitric oxide modulates synaptic vesicle docking fusion reactions.
abstract: Nitric oxide (NO) stimulates calcium-independent neurotransmitter release from synaptosomes. NO-stimulated release was found to be inhibited by Botulinum neurotoxins that inactivate the core complex of synaptic proteins involved in the docking and fusion of synaptic vesicles. In experiments using recombinant proteins, NO donors increased formation of the VAMP/SNAP-25/syntaxin 1a core complex and inhibited the binding of n-sec1 to syntaxin 1a. The combined effects of these activities is predicted to promote vesicle docking/fusion. The sulfhydryl reagent NEM inhibited the binding of n-sec1 to syntaxin 1a, while beta-ME could reverse the NO-enhanced association of VAMP/SNAP-25/syntaxin 1a. These data suggest that post-translational modification of sulfhydryl groups by a nitrogen monoxide (likely to be NO+) alters the synaptic protein interactions that regulate neurotransmitter release and synaptic plasticity.
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, California 94305, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Meffert
authors.forename: N C
authors.initials: NC
authors.lastname: Calakos
authors.forename: R H
authors.initials: RH
authors.lastname: Scheller
authors.forename: H
authors.initials: H
authors.lastname: Schulman
mesh_terms: D000818:Animals; D008565:Membrane Proteins / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology; D050765:Qa-SNARE Proteins; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects* / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D050765:Qa-SNARE Proteins; D009569:Nitric Oxide