Abstract
Many membrane-resident and secrected proteins, including growth factors and their receptors, are N-glycosylated. The initial N-glycan structure is synthesized in the endoplasmic reticulum (ER) as a branched structure on a lipid anchor (dolichol pyrophosphate) and then co-translationally, “en bloc” transferred and linked via N-acetylglucosamine to asparagine within a specific N-glycosylation acceptor sequence of the nascent recipient protein. In the ER and then the Golgi apparatus, the N-linked glycan structure is modified by hydrolytic removal of sugar residues (“trimming”) followed by re-glycosylation with additional sugar residues (“processing”) such as galactose, fucose, or sialic acid to form complex N-glycoproteins. While the sequence of the reactions leading to biosynthesis, “en bloc” transfer and processing of N-glycans is well investigated, it is still not completely understood how N-glycans affect the biological fate and function of N-glycoproteins. This review discusses the biology of N-glycoprotein synthesis, processing, and function with specific reference to the physiology and pathophysiology of the nervous system.
Keywords
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Abbreviations
- CDG:
-
Congenital disorders of glycosylation
- COG:
-
Conserved oligomeric Golgi
- dNM:
-
Deoxynojirimycin (dNJ)
- Dol-PP:
-
Dolichol pyrophosphate
- ER:
-
Endoplasmic reticulum
- ERAD:
-
ER-assisted degradation
- Gal:
-
Galactose
- GalNAc:
-
N-acetylgalactosamine
- GD2:
-
Ganglioside GD2
- GD3:
-
Ganglioside GD3
- Glc:
-
Glucose
- GlcNAc:
-
N-acetylglucosamine
- GM1:
-
Ganglioside GM1
- GM3:
-
Ganglioside GM3
- M6P:
-
Mannose-6-phosphate
- Man:
-
Mannose
- OST:
-
Oligosaccharyl transferase
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Acknowledgements
This work was supported by the National Institutes of Health R01AG034389 and the National Science Foundation (NSF1121579). We also thank the Department of Neuroscience and Regenerative Medicine (Chair Dr. Lin Mei), Georgia Regents University, Augusta, GA, for institutional support.
Compliance with Ethics Requirements The author, Dr. Erhard Bieberich, declares that he does not have any conflict of interest.
This chapter does not contain any studies with human or animal subjects.
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Bieberich, E. (2014). Synthesis, Processing, and Function of N-glycans in N-glycoproteins. In: Yu, R., Schengrund, CL. (eds) Glycobiology of the Nervous System. Advances in Neurobiology, vol 9. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1154-7_3
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