Dystroglycan Function Requires Xylosyl- and Glucuronyltransferase Activities of LARGE

Posttranslational modification of alpha-dystroglycan (alpha-DG) by the like-acetylglucosaminyltransferase (LARGE) is required for it to function as an extracellular matrix (ECM) receptor. Mutations in the LARGE gene have been identified in congenital muscular dystrophy patients with brain abnormalities. However, the precise function of LARGE remains unclear. Here we found that LARGE could act as a bifunctional glycosyltransferase, with both xylosyltransferase and glucuronyltransferase activities, which produced repeating units of [-3-xylose-alpha 1,3-glucuronic acid-beta 1-]. This modification allowed alpha-DG to bind laminin-G domain-containing ECM ligands.