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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RADZ4e10_L97MmzbviqQsy4ai5IzgmGs0Pt_2qoeUqbEk#_5 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RADZ4e10_L97MmzbviqQsy4ai5IzgmGs0Pt_2qoeUqbEk#_4 http://www.w3.org/ns/prov#value Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) mediate membrane fusion reactions in eukaryotic cells by assembling into complexes that link vesicle-associated SNAREs with SNAREs on target membranes (t-SNAREs). Many SNARE complexes contain two t-SNAREs that form a heterodimer, a putative intermediate in SNARE assembly. Individual t-SNAREs (e.g., syntaxin 1A) also regulate synaptic calcium channels and cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial chloride channel that is defective in cystic fibrosis. Whether the regulation of ion channels by individual t-SNAREs is related to SNARE complex assembly and membrane fusion is unknown. Here we show that CFTR channels are coordinately regulated by two cognate t-SNAREs, SNAP-23 (synaptosome-associated protein of 23 kDa) and syntaxin 1A. SNAP-23 physically associates with CFTR by binding to its amino-terminal tail, a region that modulates channel gating. CFTR-mediated chloride currents are inhibited by introducing excess SNAP-23 into HT29-Cl.19A epithelial cells. Conversely, CFTR activity is stimulated by a SNAP-23 antibody that blocks the binding of this t-SNARE to the CFTR amino-terminal tail. The physical and functional interactions between SNAP-23 and CFTR depend on syntaxin 1A, which binds to both proteins. We conclude that CFTR channels are regulated by a t-SNARE complex that may tune CFTR activity to rates of membrane traffic in epithelial cells. http://www.tkuhn.ch/bel2nanopub/RADZ4e10_L97MmzbviqQsy4ai5IzgmGs0Pt_2qoeUqbEk#_4 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/12209004 http://www.tkuhn.ch/bel2nanopub/RADZ4e10_L97MmzbviqQsy4ai5IzgmGs0Pt_2qoeUqbEk#_5 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RADZ4e10_L97MmzbviqQsy4ai5IzgmGs0Pt_2qoeUqbEk#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/12209004 http://www.tkuhn.ch/bel2nanopub/RADZ4e10_L97MmzbviqQsy4ai5IzgmGs0Pt_2qoeUqbEk#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RADZ4e10_L97MmzbviqQsy4ai5IzgmGs0Pt_2qoeUqbEk#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RADZ4e10_L97MmzbviqQsy4ai5IzgmGs0Pt_2qoeUqbEk#_4 http://www.tkuhn.ch/bel2nanopub/RADZ4e10_L97MmzbviqQsy4ai5IzgmGs0Pt_2qoeUqbEk#pubinfo http://www.tkuhn.ch/bel2nanopub/RADZ4e10_L97MmzbviqQsy4ai5IzgmGs0Pt_2qoeUqbEk http://purl.org/dc/terms/created 2014-07-03T14:30:05.462+02:00 http://www.tkuhn.ch/bel2nanopub/RADZ4e10_L97MmzbviqQsy4ai5IzgmGs0Pt_2qoeUqbEk http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RADZ4e10_L97MmzbviqQsy4ai5IzgmGs0Pt_2qoeUqbEk http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234