Fig. 8. Individual N-linked oligosaccharides promote different fates in the processing of CFTR. Immediately after addition of the core glycan to the nascent polypeptide chain, the outermost of the three glucose residues is removed by glucosidase I. Subsequently, glucosidase II removes the next glucose residue. The resulting monoglucosylated core glycans bind to calnexin. When glucosidase II removes the remaining glucose residue, the glycoprotein dissociates from calnexin and, if properly folded, is free to leave the ER. If the protein is incompletely folded it is reglucosylated by the UDP-glucose:glycoprotein glucosyltransferase, creating again a monoglycosylated core oligosaccharide that can bind to calnexin. Proteins that have stayed in the ER for too long and are terminally misfolded become a substrate for -mannosidase I. The trimmed oligosaccharide binds to EDEM (ER degradation-enhancing -mannosidase-like protein) and the glycoprotein is consequently directed towards ERAD (ER-associated degradation). The carbohydrate at position 900 in CFTR N894D supports the route to maturation and progress to the Golgi, whereas the oligosaccharide at asparagine residue 894 in N900D promotes degradation.