Distinctive domains and activity regulation of core fucosylation enzyme FUT8

Core fucose, a structure added to the reducing end N-acetylglucosamine of N-glycans, has been shown to regulate various physiological and pathological processes, including melanoma metastasis, exacerbation of chronic obstructive pulmonary disease, and severe outcomes in COVID-19. Recent research has shed light on regulation of the activity and subcellular localization of a1,6-fucosyltransferase (FUT8), the glycosyltransferase responsible for core fucose biosynthesis, unraveling the mechanisms for controlling core fucosylation in vivo. This review summarizes the various features of FUT8, including its domains, structures, and substrate specificity. Additionally, we discuss the potential involvement of FUT8-binding proteins, such as oligosaccharyltransferase subunits, in the regulation of FUT8 activity, substrate specificity, and the secretion of FUT8. We anticipate that this review will contribute to a deeper understanding of the control of core fucose levels in vivo and involvement of core fucosylation in FUT8-relevant functions and diseases.