Nucleocytoplasmic Glycosylation

Excerpt

The glycosylation of macromolecules is a highly compartmentalized process. Most of the enzyme donor precursors are synthesized in the cytoplasm or nucleoplasm and transferred into the secretory pathway. There they are incorporated into the glycoproteins, glycolipids, or polysaccharides that are fated for delivery to the extracellular environment or organelles such as the lysosome. In some cases, the donor sugars are transferred to intermediate lipids presented at the cytoplasmic surface of secretory pathway membranes, and subsequently flipped into the secretory pathway for final incorporation into glycoconjugates. In other cases, polysaccharides are synthesized at the cytoplasmic surface of the plasma membrane and simultaneously translocated to the cell surface. Thus the cytoplasm has a key role in the assembly of glycans that are, however, destined to function outside of the cytoplasm. In addition, entirely different glycosyltransferases exist in the cytoplasm or nucleus to glycosylate proteins and lipids that remain to function in the cytoplasm or nucleoplasm. There is also evidence for cytoplasmic and nuclear glycoconjugates that have acquired secretory pathway–type glycans by unexplained mechanisms. The origin and role of these nucleocytoplasmic glycoconjugates, mainly glycoproteins, are the focus of this chapter. We begin with examples of monoglycosylation, including both endogenous processes and those associated with parasitism, and note that one form, O-linked β-N-acetylglucosamine (O-β-GlcNAc), is so prevalent that an entire chapter is devoted to it (Chapter 19). We then continue to complex glycans and glycosylation associated with mitochondria and chloroplasts and conclude with an assessment of nucleocytoplasmic carbohydrate binding proteins that may serve as glycan readers.