Loss of core fucosylation in both ST6GAL1 and its substrate enhances glycoprotein sialylation in mice

Fucosyltransferase 8 (FUT8) and beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1) are glycosyltransferases (GTases) that catalyze alpha1,6-fucosylation and alpha2,6-sialylation, respectively, in the mammalian N-glycosylation pathway. They are aberrantly expressed in various human diseases. FUT8 is non-glycosylated but is responsible for the fucosylation of ST6GAL1. However, the mechanism for the interaction between these two enzymes is unknown. In this study, we show that serum levels of alpha2,6-sialylated N-glycans are increased in Fut8-/- mice, whereas the mRNA and protein levels of ST6GAL1 are unchanged in mouse live tissues. The level of alpha2,6-sialylation on IgG was also enhanced in Fut8-/- mice along with ST6GAL1 catalytic activity increase in both serum and liver. Moreover, it was observed that ST6GAL1 prefers non-fucosylated substrates. Interestingly, increased core fucosylation accompanied by a reduction in alpha2,6-sialylation, was detected in rheumatoid arthritis (RA) patient serum. These findings provide new insight into the interactions between FUT8 and ST6GAL1.