O -Mannosyl Phosphorylation of Alpha-Dystroglycan Is Required for Laminin Binding

Abstract

Modifying Protein Modification Alpha-dystroglycan (α-DG) is a cell-surface receptor that anchors the basal lamina to the sarcolemma by binding proteins containing laminin-G domains. This binding is essential for protecting muscle from contraction-induced injury, and defective binding is thought to cause a subclass of congenital muscular dystrophy (CMD) in humans. Mutations in six (putative) glycosyltransferase genes have been identified in patients with CMD, suggesting that glycosylation of α-DG may confer the ability to bind laminin. Despite extensive efforts for over 20 years, the actual laminin-binding moiety has remained unclear. Now, Yoshida-Moriguchi et al. (p. 88 ) have identified a phosphorylated O -mannosyl glycan on α-DG. This modification occurred in the Golgi via an unidentified kinase and was required for the maturation of α-DG into its laminin-binding form.