Recent advancements in understanding mammalian O-mannosylation

The post-translational glycosylation of select proteins by O-linked mannose (O-mannose or O-man) is a conserved modification from yeast to humans and has been shown to be necessary for proper development and growth. The most well studied O-mannosylated mammalian protein is α-dystroglycan (α-DG). Hyp...

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Bibliographic Details
Published in:Glycobiology (Oxford) 2017-09, Vol.27 (9), p.806-819
Main Authors: Sheikh, M Osman, Halmo, Stephanie M, Wells, Lance
Format: Article
Language:English
Subjects:
Animals
Arenavirus - metabolism
Dystroglycans - chemistry
Dystroglycans - genetics
Dystroglycans - metabolism
Evolution, Molecular
Glycosylation
Glycosyltransferases - genetics
Glycosyltransferases - metabolism
Humans
Mammals
Mannose - chemistry
Mannose - metabolism
Muscular Dystrophies - genetics
Muscular Dystrophies - metabolism
Muscular Dystrophies - pathology
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Protein Processing, Post-Translational
Receptors, Virus - chemistry
Receptors, Virus - genetics
Receptors, Virus - metabolism
Review
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Summary:The post-translational glycosylation of select proteins by O-linked mannose (O-mannose or O-man) is a conserved modification from yeast to humans and has been shown to be necessary for proper development and growth. The most well studied O-mannosylated mammalian protein is α-dystroglycan (α-DG). Hypoglycosylation of α-DG results in varying severities of congenital muscular dystrophies, cancer progression and metastasis, and inhibited entry and infection of certain arenaviruses. Defects in the gene products responsible for post-translational modification of α-DG, primarily glycosyltransferases, are the basis for these diseases. The multitude of clinical phenotypes resulting from defective O-mannosylation highlights the biomedical significance of this unique modification. Elucidation of the various O-mannose biosynthetic pathways is imperative to understanding a broad range of human diseases and for the development of novel therapeutics. In this review, we will focus on recent discoveries delineating the various enzymes, structures and functions associated with O-mannose-initiated glycoproteins. Additionally, we discuss current gaps in our knowledge of mammalian O-mannosylation, discuss the evolution of this pathway, and illustrate the utility and limitations of model systems to study functions of O-mannosylation.
ISSN:0959-6658
1460-2423
DOI:10.1093/glycob/cwx062