Figure 1.

Overview of human N- and O-glycosylation in the Golgi apparatus. On the left side, the synthesis of a human glycoprotein with several relevant complex-type N-glycans is shown. In the cis Golgi, mannosidase I (ManI) activity leads to a Man₅GlcNAc₂ that can be further modified in the medial Golgi. N-acetylglucosaminyltransferase I (GnTI) activity commits the glycan to the complex or hybrid type. Mannosidase II (ManII) activity, followed by several N-acetylglucosaminyltransferases then further commits the glycan to the complex type. If only N-acetylglucosaminyltransferases II (GnTII) acts on it, the result is a biantennary complex type N-glycan. GnTIV and/or GnTV activity then generates different triantennary or a tetraantennary complex type glycan. Fucosyltransferase VIII (FucTVIII) can act on any complex or hybrid type glycan to add a core α-1,6-fucose in the medial Golgi. Afterward, in the trans Golgi, galactosyltransferases (GalT), fucosyltransferases (FucT), sialyltransferases (SiaT) or a combination of GnTs and GalTs synthesize different capping moieties (sialylation, poly-LacNAc repeats, Lewis antigens) on N-glycans

The right side of the figure shows mucin-type O-glycosylation biosynthesis. Polypeptide-GalNAc-transferases (ppGalNAcTs) initiate O-glycosylation in the cis Golgi, which is followed by the action of one or two core synthesizing enzymes: core 1 galactosyltransferase (C1GalT), core 2 N-acetylglucosaminidase I, II or III (C2GnTI/II/III) and core 3 N-acetylglucosaminidase (C3GnT), resulting in the synthesis of four so-called core structures. Core 1 and 2 are common, while core 3 and 4 have a restricted expression pattern. Two SiaT activities in particular (ST6GalNAc and ST3Gal) can add N-Acetylneuraminic acid to the Tn antigen or core 1 (T antigen) to generate the sialyl-Tn or sialyl-T antigen (STn or ST antigen). Several GalTs, GnTs, FucTs and SiaTs can act on the core structures to introduce further branching and terminating structures (not shown). Note that four more core structures (core 5–8) are known, but since their occurrence is extremely rare, they are not shown here. This figure has been adapted from De Wachter et al. with permission.⁷