title: Regulation of CFTR chloride channels by syntaxin and Munc18 isoforms.
abstract: The cystic fibrosis gene encodes a cyclic AMP-gated chloride channel (CFTR) that mediates electrolyte transport across the luminal surfaces of a variety of epithelial cells. The molecular mechanisms that modulate CFTR activity in epithelial tissues are poorly understood. Here we show that CFTR is regulated by an epithelially expressed syntaxin (syntaxin 1A), a membrane protein that also modulates neurosecretion and calcium-channel gating in brain. Syntaxin 1A physically interacts with CFTR chloride channels and regulates CFTR-mediated currents both in Xenopus oocytes and in epithelial cells that normally express these proteins. The physical and functional interactions between syntaxin 1A and CFTR are blocked by a syntaxin-binding protein of the Munc18 protein family (also called n-Secl). Our results indicate that CFTR function in epithelial cells is regulated by an interplay between syntaxin and Munc18 isoforms.
authors.affiliation: Department of Physiology and Biophysics, Gregory Fleming James Cystic Fibrosis Research Center, Birmingham, Alabama 35294, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Naren
authors.forename: D J
authors.initials: DJ
authors.lastname: Nelson
authors.forename: W
authors.initials: W
authors.lastname: Xie
authors.forename: B
authors.initials: B
authors.lastname: Jovov
authors.forename: J
authors.initials: J
authors.lastname: Pevsner
authors.forename: M K
authors.initials: MK
authors.lastname: Bennett
authors.forename: D J
authors.initials: DJ
authors.lastname: Benos
authors.forename: M W
authors.initials: MW
authors.lastname: Quick
authors.forename: K L
authors.initials: KL
authors.lastname: Kirk
mesh_terms: D000818:Animals; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000166:cytology; D003550:Cystic Fibrosis; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007536:Isomerism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009865:Oocytes; D018408:Patch-Clamp Techniques; D050765:Qa-SNARE Proteins; D011994:Recombinant Proteins; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins; D014981:Xenopus; D029867:Xenopus Proteins
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D008565:Membrane Proteins; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D011994:Recombinant Proteins; C494212:STX1A protein, human; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins; D029867:Xenopus Proteins; C497933:Xunc18 protein, Xenopus; D019005:Cystic Fibrosis Transmembrane Conductance Regulator