The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) plays a crucial role in mediating duodenal bicarbonate (HCO(3)(-)) secretion (DBS). Although impaired DBS is observed in CF mutant mice and in CF patients, which would predict increased ulcer susceptibility, duodenal injury is rarely observed in CF patients and is reduced in CF mutant mice. To explain this apparent paradox, we ...

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride ion channel that also serves as a receptor for entry of Pseudomonas aeruginosa and Salmonella enterica serovar Typhi into epithelial cells. To evaluate heterogeneity in CFTR protein expression in cultured cells and the effect of heterogeneity on internalization of different P. aeruginosa and serovar Typhi strains, we u...

PURPOSE To determine the effects of contact lenses (CLs) and Pseudomonas aeruginosa (PA) infection on localization of cystic fibrosis transmembrane conductance regulator (CFTR) on corneal surface epithelial cells and the association between lipid raft formation and CFTR in mediating PA binding and internalization in ocular surface epithelium. METHODS CFTR immunolocalization was evaluated in v...

We have shown that cystic fibrosis transmembrane conductance regulator (CFTR) is involved in ATP release from skeletal muscle at low pH. These experiments investigate the signal transduction mechanism linking pH depression to CFTR activation and ATP release, and evaluate whether CFTR is involved in ATP release from contracting muscle. Lactic acid treatment elevated interstitial ATP of buffer-pe...

The majority of cystic fibrosis (CF)-causing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) lead to the misfolding, mistrafficking, and degradation of the mutant protein. Inhibition of degradation does not effectively increase the amount of trafficking competent CFTR, but typically leads to increased ER retention of misfolded forms. Thus, the initial off pathway ste...

The CFTR (cystic fibrosis transmembrane conductance regulator) gene is a tightly regulated and differentially expressed transcript in many mucosal epithelial cell types. It appears that DNA sequence variations alone do not explain CFTR-related gastrointestinal disease patterns and that epigenetic modifiers influence CFTR expression. Our aim was to characterize the native chromatin environment i...

BACKGROUND Dysfunction in cystic fibrosis transmembrane conductance regulator (CFTR) can be elicited by cigarette smoke and is observed in patients with chronic bronchitis. We have previously demonstrated in human airway epithelial cell monolayers that roflumilast, a clinically approved phosphodiesterase 4 inhibitor that reduces the risk of exacerbations in chronic obstructive pulmonary disease...

Although the cystic fibrosis transmembrane conductance regulator (CFTR) is primarily implicated in the regulation of plasma-membrane chloride permeability, immunolocalization and functional studies indicate the presence of CFTR in the endosomal compartment. The mechanism of CFTR delivery from the cell surface to endosomes is not understood. To delineate the internalization pathway, both the rat...

Cystic fibrosis (CF) is a multifactorial disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene ( CFTR), which encodes a cAMP-dependent Cl (-) channel. The most frequent mutation, F508del, leads to the synthesis of a prematurely degraded, otherwise partially functional protein. CFTR is expressed in many epithelia, with major consequences in the airways of pa...

Most mutants of the cystic fibrosis transmembrane conductance regulator (CFTR) that cause severe symptoms of cystic fibrosis do not reach the cell surface because they are defective in folding. Many CFTR folding mutants, however, including the DeltaF508 mutant found in more than 90% of cystic fibrosis patients, are potentially functional at the cell surface if they can be induced to fold correc...