title: Dissecting the molecular basis of the role of the O-mannosylation pathway in disease: α-dystroglycan and forms of muscular dystrophy.
abstract: Dystroglycanopathies form a subgroup of muscular dystrophies that arise from defects in enzymes that are implicated in the recently elucidated O-mannosylation pathway, thereby resulting in underglycosylation of α-dystroglycan. The emerging identification of additional brain proteins modified by O-mannosylation provides a broader context for interpreting the range of neurological consequences associated with dystroglycanopathies. This form of glycosylation is associated with protein mucin-like domains that present numerous serine and threonine residues as possible sites for modification. Furthermore, the O-Man glycans coexist in this region with O-GalNAc glycans (conventionally associated with such protein sequences), thus resulting in a complex glycoconjugate landscape. Sorting out the relationships between the various molecular defects in glycosylation and the modes of disease presentation, as well as the regulatory interplay among the O-Man glycans and the effects on other modes of glycosylation in the same domain, is challenging. Here we provide a perspective on chemical biology approaches employing synthetic and analytical methods to address these questions.
authors: Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602 (USA).
authors: David
authors: D
authors: Live
authors: Lance
authors: L
authors: Wells
authors: Geert-Jan
authors: GJ
authors: Boons
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002240:Carbohydrate Sequence; D049030:Dystroglycans / Q000737:chemistry / Q000378:metabolism*; D006001:Glycoconjugates / Q000737:chemistry / Q000378:metabolism*; D006020:Glycopeptides / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008358:Mannose / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000201:enzymology / Q000378:metabolism* / Q000628:therapy
chemical_list: D006001:Glycoconjugates; D006020:Glycopeptides; D049030:Dystroglycans; D008358:Mannose
keywords: alpha-dystroglycan; carbohydrates; dystroglycanopathies; glycopeptides; muscular dystrophy; protein O-mannosylation