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SGK1 Increases Plasma Membrane CFTR in Human Airway Epithelial Cells
Author(s) -
Bomberger Jennifer,
Sato Denry,
Coutermarsh Bonita,
Barnaby Roxanna,
Chapline M Christin,
Stanton Bruce
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.610.15
Subject(s) - sgk1 , apical membrane , cystic fibrosis transmembrane conductance regulator , microbiology and biotechnology , endosome , chloride channel , endocytic cycle , intracellular , chemistry , epithelial sodium channel , endocytosis , biology , kinase , cystic fibrosis , cell , membrane , biochemistry , genetics , organic chemistry , sodium
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a cyclic AMP‐regulated chloride channel and a regulator of other ion channels and transporters in epithelial tissues. CFTR rapidly cycles between the apical plasma membrane, early endosomes, and recycling endosomes. However, little is known about the regulation of CFTR endocytic trafficking. Thus, understanding the protein‐protein interactions that regulate the intracellular trafficking of CFTR is critical. We recently reported that serum‐ and glucocorticoid‐regulated kinase 1 (SGK1) stimulates CFTR Cl currents in Xenopus oocytes by increasing the number of channels in the plasma membrane. In this study, we examined the effects of SGK1 on CFTR in polarized human airway epithelial cells (WT‐CFTR CFBE41o‐ cells). Dexamethasone (50 nM) rapidly (30–60 minutes) increased SGK1 mRNA and protein abundance in a time‐dependent manner. The increase in SGK1 protein was followed by an increase in CFTR in the apical membrane and total cell lysates. Overexpression of a constitutive‐active SGK, SGK‐S422D, increased apical membrane CFTR, while siRNA knockdown of SGK1 reduced the dexamethasone‐stimulated increase in apical membrane CFTR. Finally, a dominant negative SGK1 (K127N) had no effect on CFTR expression in the apical membrane. These studies demonstrate that SGK1 increases the apical membrane abundance of CFTR in human airway epithelial cells.