Effects of C-terminal deletions on cystic fibrosis transmembrane conductance regulator function in cystic fibrosis airway epithelia
LS Ostedgaard, C Randak, T Rokhlina… - Proceedings of the …, 2003 - National Acad Sciences
LS Ostedgaard, C Randak, T Rokhlina, P Karp, D Vermeer, KJ Ashbourne Excoffon…
Proceedings of the National Academy of Sciences, 2003•National Acad SciencesTo 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 P SD-95/D iscs-large/Z O-1 (PDZ)-
interacting motif nor other C-terminal sequences were absolutely required for apical …
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 P SD-95/D iscs-large/Z O-1 (PDZ)-
interacting motif nor other C-terminal sequences were absolutely required for apical …
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.
National Acad Sciences