O-Glycan Synthesis and Modification

In mammals, there are a several different types of O-glycosylation.  These include mucin and nonmucin O-glycans.

Mucin glycoproteins:

• Tend to be heavily O-glycosylated.
• Are found in mucous secretions and as transmembrane glycoproteins on the cell surface.
• Addition of O-glycans on the glycoprotein is initiated in the Golgi apparatus.
• Synthesis starts with the addition of an N-acetylgalactosamine (GalNAc) residue to the OH of either a serine or threonine on the glycoprotein.
• There are 8 O-glycan core structures found in mucins (Table 1).
• The growing glycan chain is extended with the addition of other monosaccharides (1, Fig. 1)

O-glycan	Structure
Core 1 or T antigen
Core 2
Core 3
Core 4

Non-mucin glycans are more varied:

• O-fucose and O-glucose residues are:
  • transferred to consensus cysteine in certain proteins in the ER
  • essential for protein interaction and signal transduction (2)

• O-GlcNAc can modify nuclear and cytosolic proteins. This:
  • occurs at serine or threonine residues
  • is a highly dynamic modification
  • plays an important role in cell signaling
  • modulates protein function much like phosphorylation (3, Fig. 2)
  • can compete directly with phosphate residues for occupancy of serine or threonine residues on the protein

References

1. Gill DJ, et al. (2011) Trends Cell Biol. 21(3):149-58. PMID: 21145746
2. Luther KB, Haltiwanger RS. (2009) Int J Biochem Cell Biol. 41(5):1011-24. PMID: 18952191
3. Zeidan Q, Hart GW. (2010) J Cell Sci. 123(Pt 1):13-22. PMID: 20016062