The Glycobiology of Cystic Fibrosis

Cystic fibrosis (CF), the most common lethal genetic disease of Caucasians, is characterized by pathology to the exocrine organs, especially the lungs which are the site of most of the morbidity and mortality of the disease. The gene causing CF was defined more than a decade ago and a deletion of F508 has been shown to be the most common mutation. The gene product the cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl- channel on the apical surface of epithelial cells and has been extensively studied. It is a large glycoprotein but the glycosylation has not yet been defined. On the other hand, examination of glycosylation on the surface of CF airway epithelial cells has shown a glycophenotype, which is usually expressed as increased fucosyl residues and / or decreased sialic acid. Studies have shown a direct relationship of CFTR to the CF glycophenotype in airway epithelial cells. The terminal glycosyltransferases which are responsible for the CF glycophenotype have been studied. A difference in these enzymes and the mRNA expression was not sufficient to account for the altered surface glycoproteins of CF and non CF cells. It may be possible that a compartmental difference in the Golgi between CF and non CF glycosyltransferases may be responsible for the CF glycophenotype.