DEFECTIVE ACIDIFICATION OF THE BIOSYNTHETIC-PATHWAY IN CYSTIC-FIBROSIS

Cystic fibrosis is associated with defective epithelial sodium chlorid e and fluid secretion in epithelia. In addition, there is widespread r eductions in sialylation of secreted proteins and increases in the sul fation and fucosylation of mucus glycoproteins. The major morbidity in the disease is due to the colonization of respiratory epithelia by Ps eudomonas. The cystic fibrosis gene (CFTR) is a cyclic AMP activated C l channel, which when mutated is retained in the endoplasmic reticulum . We postulate that this Cl channel is responsible for effective acidi fication of the Golgi. In CF cells, we demonstrate the Golgi pH is hig her than in normal cells and suggest that the abnormalities in glycopr otein biosynthesis is due to changes in the kinetics of sialyl transfe rase, a pH sensitive enzyme. Defects in sialylation also result in dec reased sialylation of glycolipids and asialogangliosides are potential Pseudomonas receptors.