Biosynthesis and Regulation of Laminin-Binding O-Mannosyl Glycans Related to Muscular Dystrophy.

Glycosylation is an important post-translational protein modification involved in various biological processes. Glycans are divided into two types: Asn-linked N-glycans and Ser/Thr-linked O-glycans. O-mannosyl glycans are a unique group of O-glycans in mammals that play critical roles in the skeletal muscle and the brain. The plasma membrane-localized glycoprotein α-dystroglycan (α-DG) is modified with a laminin-binding O-mannosyl glycan. Defects in this glycan synthesis result in the loss of α-DG laminin-binding and cause a group of congenital muscular dystrophies with neuronal abnormalities, collectively termed dystroglycanopathy. Considerable efforts have been devoted to elucidating the laminin-binding O-mannosyl glycan structure. Recently, the complete structure of the glycan and its biosynthetic enzymes have been revealed. Pathological analyses of dystroglycanopathy in patients and mouse models have clarified the physiological functions of this glycan. In this review, we describe the structures, biosynthetic mechanisms, and functions of O-mannosyl glycans in mammals, with a focus on the laminin-binding O-mannosyl glycan. In addition, we summarize recent progress in the regulatory mechanisms of laminin-binding O-mannosyl glycan biosynthesis.