O-Mannose and O-N-acetyl galactosamine glycosylation of mammalian α-dystroglycan is conserved in a region-specific manner

• Published in: Glycobiology (Oxford) 2012-11, Vol.22 (11), p.1413-1423
• Main Authors: Gomez Toledo, Alejandro, Raducu, Madalina, Cruces, Jesús, Nilsson, Jonas, Halim, Adnan, Larson, Göran, Rüetschi, Ulla, Grahn, Ammi
• Format: Article
• Language: English
• Subjects: Acetylgalactosamine - metabolism; alpha-dystroglycan; Animals; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; Dystroglycans - chemistry; Dystroglycans - metabolism; fkrp gene; girdle muscular-dystrophy; glycan; glycoproteomics; Glycosylation; Humans; laminin-binding; mammalian; Mannose - metabolism; mannosylation; mass spectrometry; Mice; Muscle, Skeletal - metabolism; mutations; O-glycosylation; peripheral-nerve; phenotype; protein gene; Protein Structure, Tertiary; Rabbits; skeletal-muscle; Species Specificity; structures
• ISSN: 0959-6658; 1460-2423
• DOI: 10.1093/glycob/cws109

Defects in the O-linked glycosylation of the peripheral membrane protein α-dystroglycan (α-DG) are the main cause of several forms of congenital muscular dystrophies and thus the characterization of the glycosylation of α-DG is of great medical importance. A detailed investigation of the glycosylation pattern of the native α-DG protein is essential for the understanding of the biological processes related to human disease in which the protein is involved. To date, several studies have reported novel O-glycans and attachment sites on the mucin-like domain of mammalian α-DG with both similar and contradicting glycosylation patterns, indicating the species-specific O-glycosylation of mammalian α-DG. By applying a standardized purification scheme and subsequent glycoproteomic analysis of native α-DG from rabbit and human skeletal muscle biopsies and from cultured mouse C2C12 myotubes, we show that the O-glycosylation patterns of the mucin-like domain of native α-DG are conserved among mammalians in a region-specific manner.