GLUCOSE TRIMMING AND REGLUCOSYLATION DETERMINE GLYCOPROTEIN ASSOCIATION WITH CALNEXIN IN THE ENDOPLASMIC-RETICULUM

To determine the role of N-linked oligosaccharides in the folding of g lycoproteins, we analyzed the processing of in vitro translated influe nza hemagglutinin (HA) in dog pancreas microsomes. We found that bindi ng to calnexin, a membrane-bound molecular chaperone, was specific to molecules that possessed monoglucosylated core glycans. In the microso mes, these were generated either by glucose removal from the original triglucosylated core oligosaccharide by glucosidases I and II or by re glucosylation of already unglucosylated high mannose glycans. Release of fully folded HA from calnexin required the removal of the remaining glucose by glucosidase II. The results provided an explanation for tr imming and reglucosylation activities in the endoplasmic reticulum and established a direct correlation between glycosylation and folding.