Regulation of CFTR expression and function by NOS isoforms

Background The cystic fibrosis transmembrane conductance regulator (CFTR) is the gene of interest in the eponymous disease, cystic fibrosis (CF). CFTR is expressed in epithelial cells and functions as a chloride channel. Several hundred mutations are known to occur in CF patients, but the most prevalent mutation is the deletion of phenylalanine at position 508 (ΔF508). Although the mutated protein is retained in the endoplasmic reticulum, the channel has been shown to be at least in part functional. A possible strategy for the treatment of CF therefore aims at facilitating surface expression by e.g. increasing total protein expression or by chaperoning the protein on its route from the endoplasmic reticulum to the cell surface. Polymorphisms in nitric oxide synthase (NOS) have been shown to influence disease severity in CF patients. Insights into the molecular mechanisms underlying the disease modifying effect of NOS will not only help understanding variation in the clinical course of cystic fibrosis but it may also provide information that can be exploited to improve and individualize treatment strategies for CF patients.