O-Glycan Synthesis and Modification

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The Golgi apparatus is also where O-glycans are built. In mammals, their synthesis starts by the addition of a GalNAc residue, and is extended step by step by the addition of other monosaccharides (1, Fig. 1). Other types of O-glycans are attached in the ER, for instance O-fucose and O-glucose residues are transferred to consensus cysteines in certain proteins, a modification which is essential for protein interaction and signal transduction (2).

Figure 1: A representation of the synthesis of O-glycans in the Golgi. Glycosyltransferases use activated sugars (nucleotide-sugars) as donors for the extension reactions.

Glycosylation is not limited to the secretory pathway, nuclear and cytosolic proteins can be modified with O-GlcNAc at serine or threonine residues. This is a highly dynamic modification with an important role in signaling: the single sugar is attached and removed in cycles, modulating protein function much like phosphorylation (3) (Fig. 2). In fact in some cases O-GlcNAc competes directly with phosphate for occupancy of serine and threonine residues on the protein.

Figure 2: Demonstrates the transient O-GlcNAc modification of some proteins. O-GlcNAc transferase (OGT) transfers a GlcNAc residue from UDP-GlcNAc to a serine or threonine in the target 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