The cystic fibrosis transmembrane conductance regulator: an intriguing protein with pleiotropic functions

Abstract

Cystic fibrosis is a frequent autosomal recessive disorder that is caused by the malfunctioning of a small chloride channel, the cystic fibrosis transmembrane conductance regulator. The protein is found in the apical membrane of epithelial cells lining exocrine glands. Absence of this channel results in imbalance of ion concentrations across the cell membrane. As a result, fluids secreted through these glands become more viscous and, in the end, ducts become plugged and atrophic. Little is known about the pathways that link the malfunctioning of the CFTR protein with the observed clinical phenotype. Moreover, there is no strict correlation between specific CFTR mutations and the CF phenotype. This might be explained by the fact that environmental and additional genetic factors may influence the phenotype. The CFTR protein itself is regulated at the maturational level by chaperones and SNARE proteins and at the functional level by several protein kinases. Moreover, CFTR functions also as a regulator of other ion channels and of intracellular membrane transport processes. In order to be able to function as a protein with pleiotropic actions, CFTR seems to be linked with other proteins and with the cytoskeleton through interaction with PDZ-domain-containing proteins at the apical pole of the cell. Progress in cystic fibrosis research is substantial, but still leaves many questions unanswered.

The role for neutrophil extracellular traps in cystic fibrosis autoimmunity

“…Mutations in the CF transmembrane conductance regulator (CFTR) gene disrupt CFTR-controlled secretion of bicarbonate and chloride across airway epithelial cells (3). This impairment in ion transport across the epithelium enhances mucus viscosity and interferes with mucociliary clearance, thereby creating an environment susceptible to bacterial infection (4,5).…”

Cystic fibrosis -- therapeutic challenge in cystic fibrosis children

“…Thus, if the CFTR is not functioning, the bacteria in the airway lumen are free to multiply. The possible role of CFTR in lipid metabolism and the elevated resting energy expenditure is not fully understood (10,11). …”

CCL Chemokines Levels in Tear Fluid of Patients with Cystic Fibrosis

“…Although CFTR functions mainly as a chloride channel, it has many other regulatory roles, including inhibition of sodium transport through the epithelial sodium channel, regulation of the outwardly rectifying chloride channel, regulation of ATP channels, regulation of intracellular vesicle transport, acidification of intracellular organelles, and inhibition of endogenous calcium-activated chloride channels (O'Sullivan & Freedman, 2009;Reisin et al, 1994;Schwiebert et al, 1995;Stutts et al, 1995;Vankeerberghen et al, 2002;Mehta, 2005). CFTR is also involved in bicarbonate-chloride exchange.…”