Biosynthetic Pathway of O-Mannosyl Glycan in Mammals

Abstract

Glycosylation is the most frequent modification of proteins and is important for many ligand-receptor interactions.We have attempted to demonstrate the biosynthetic pathway and the function of O-mannosyl glycan since 1997 when the O-mannosyl glycan structure was identified. In this study, we have identified and characterized glycosyltransferases, POMT1, POMT2 and POMGnT1. Mutations in POMT1, POMT2 or POMGnT1 can lead to a congenital muscular dystrophy with abnormal neuronal migration. Our findings indicate that O-mannosyl glycan plays an important role in muscle and brain development. This review briefly outlines the biosynthetic mechanism of O-mannosyl glycan in mammals.

Chemoenzymatic synthesis of α-dystroglycan core M1 O-mannose glycans

“…1–4 In addition to conventional N-glycans and O-GalNAc glycans, the “uncommon” O-mannose glycans abundant on the mucin domain of α-DG play essential roles in muscle structure and function. Defects in O-mannosylation can cause several congenital muscular dystrophies (CMDs) and promote metastasis of many types of cancers.…”

“…a-Dystroglycan (a-DG), a heavily glycosylated protein found in muscle and brain tissue, is a key component of the dystroglycanglycoprotein complex that links the extracellular matrix to the intracellular cytoskeleton. [1][2][3][4] In addition to conventional N-glycans and O-GalNAc glycans, the ''uncommon'' O-mannose glycans abundant in the mucin domain of a-DG play essential roles in muscle structure and function. Defects in O-mannosylation can cause several congenital muscular dystrophies (CMDs) and promote metastasis of many types of cancers.…”

“…1 Although the biological significance of O-mannose glycans has been well documented, the biosynthetic pathway and the precise function of this diverse glycan library have not yet been fully understood. [1][2][3][4][5][6] Therefore, the synthesis of structurally well-defined O-mannose glycans in sufficient amount will not only provide carbohydrate standards for the identification of these glycans from natural sources, but also provide the probes for the elucidation of their biosynthetic pathway and structureactivity relationship (SAR) studies.…”