Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
 free
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
 free
 free
 
English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve
Pubget Overpricing |  
lüll
Serum and glucocorticoid-inducible kinase1 increases plasma membrane wt-CFTR in human airway epithelial cells by inhibiting its endocytic retrieval Bomberger JM; Coutermarsh BA; Barnaby RL; Sato JD; Chapline MC; Stanton BAPLoS One 2014[]; 9 (2): e89599BACKGROUND: Chloride (Cl) secretion by the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) located in the apical membrane of respiratory epithelial cells plays a critical role in maintenance of the airway surface liquid and mucociliary clearance of pathogens. Previously, we and others have shown that the serum and glucocorticoid-inducible kinase-1 (SGK1) increases wild type CFTR (wt-CFTR) mediated Cl transport in Xenopus oocytes by increasing the amount of wt-CFTR protein in the plasma membrane. However, the effect of SGK1 on the membrane abundance of wt-CFTR in airway epithelial cells has not been examined, and the mechanism whereby SGK1 increases membrane wt-CFTR has also not been examined. Thus, the goal of this study was to elucidate the mechanism whereby SGK1 regulates the membrane abundance of wt-CFTR in human airway epithelial cells. METHODS AND RESULTS: We report that elevated levels of SGK1, induced by dexamethasone, increase plasma membrane abundance of wt-CFTR. Reduction of SGK1 expression by siRNA (siSGK1) and inhibition of SGK1 activity by the SGK inhibitor GSK 650394 abrogated the ability of dexamethasone to increase plasma membrane wt-CFTR. Overexpression of a constitutively active SGK1 (SGK1-S422D) increased plasma membrane abundance of wt-CFTR. To understand the mechanism whereby SGK1 increased plasma membrane wt-CFTR, we examined the effects of siSGK1 and SGK1-S442D on the endocytic retrieval of wt-CFTR. While siSGK1 increased wt-CFTR endocytosis, SGK1-S442D inhibited CFTR endocytosis. Neither siSGK1 nor SGK1-S442D altered the recycling of endocytosed wt-CFTR back to the plasma membrane. By contrast, SGK1 increased the endocytosis of the epidermal growth factor receptor (EGFR). CONCLUSION: This study demonstrates for the first time that SGK1 selectively increases wt-CFTR in the plasma membrane of human airway epithelia cells by inhibiting its endocytic retrieval from the membrane.|*Endocytosis[MESH]|Benzoates/pharmacology[MESH]|Bridged Bicyclo Compounds, Heterocyclic/pharmacology[MESH]|Cell Line[MESH]|Cell Membrane/*metabolism[MESH]|Cell Polarity[MESH]|Cystic Fibrosis Transmembrane Conductance Regulator/*metabolism[MESH]|Dexamethasone/pharmacology[MESH]|Endosomes/metabolism[MESH]|Enzyme Induction[MESH]|Epithelial Cells/*enzymology[MESH]|ErbB Receptors/metabolism[MESH]|Gene Expression/drug effects[MESH]|Glucocorticoids/pharmacology[MESH]|Humans[MESH]|Immediate-Early Proteins/antagonists & inhibitors/*physiology[MESH]|Protein Serine-Threonine Kinases/antagonists & inhibitors/*physiology[MESH]|Protein Transport[MESH]|Respiratory Mucosa/metabolism[MESH] |
