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Synthesis, Processing, and Function of N-glycans in N-glycoproteins

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Glycobiology of the Nervous System

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 9))

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.

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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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  1. Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, 1120 15th Street Room CA4012, Augusta, GA, 30912, USA

    Erhard Bieberich

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  1. Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, USA

    Robert K. Yu

  2. Department of Biochemistry and Molecular Biology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, USA

    Cara-Lynne Schengrund

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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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