N-Glycan Branching and Its Biological Significance

Abstract

Mammalian complex N-glycans, first biosynthesized as biantennary glycans, are often modified further by specific GlcNAc transferases (GnTs) and the fucosyltransferase, FUT8, to have multiple branches. Gene-deficient mice for most of these enzymes have been generated, and analysis of these mice has revealed the physiological functions and pathological roles of the N-glycan branches. Loss of each branch leads to a different phenotype in mice, some of which are similar to human disorders, such as diabetes and lung emphysema, indicating that each branch has intrinsic functions in vivo. The defects in these knockout mice are often caused by impaired functions of a specific target protein, which would carry a specific branch on its N-glycan in wild-type mice. In this chapter, biosynthetic pathways and the biological significance of mammalian N-glycan branching are summarized. Studies of pathological/physiological roles of N-glycan branching will offer new therapeutic strategies or biomarkers for human diseases targeting glycan branching.