title: Effects of C-terminal deletions on cystic fibrosis transmembrane conductance regulator function in cystic fibrosis airway epithelia.
abstract: To better understand the function of the conserved C terminus of the cystic fibrosis (CF) transmembrane conductance regulator, we studied constructs containing deletions in the C-terminal tail. When expressed in well differentiated CF airway epithelia, each construct localized predominantly to the apical membrane and generated transepithelial Cl(-) current. The results suggested that neither the C-terminal PSD-95/Discs-large/ZO-1 (PDZ)-interacting motif nor other C-terminal sequences were absolutely required for apical expression in airway epithelia. Surprisingly, deleting an acidic cluster near the C terminus reduced both channel opening rate and transepithelial Cl(-) transport, indicating that it influences channel gating. These results may help explain the relative paucity of CF-associated mutations in the C terminus.
authors.affiliation: Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Lynda S
authors.initials: LS
authors.lastname: Ostedgaard
authors.forename: Christoph
authors.initials: C
authors.lastname: Randak
authors.forename: Tatiana
authors.initials: T
authors.lastname: Rokhlina
authors.forename: Philip
authors.initials: P
authors.lastname: Karp
authors.forename: Daniel
authors.initials: D
authors.lastname: Vermeer
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Ashbourne Excoffon
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welsh
mesh_terms: D000595:Amino Acid Sequence; D002712:Chlorides / Q000378:metabolism; D003550:Cystic Fibrosis / Q000235:genetics / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells; D006801:Humans; D007150:Immunohistochemistry; D017136:Ion Transport; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D018408:Patch-Clamp Techniques; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014132:Trachea / Q000473:pathology*
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator