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

+ See all authors and affiliations

Science  01 Jan 2010:
Vol. 327, Issue 5961, pp. 88-92
DOI: 10.1126/science.1180512

You are currently viewing the abstract.

View Full Text


Alpha-dystroglycan (α-DG) is a cell-surface glycoprotein that acts as a receptor for both extracellular matrix proteins containing laminin-G domains and certain arenaviruses. Receptor binding is thought to be mediated by a posttranslational modification, and defective binding with laminin underlies a subclass of congenital muscular dystrophy. Using mass spectrometry– and nuclear magnetic resonance (NMR)–based structural analyses, we identified a phosphorylated O-mannosyl glycan on the mucin-like domain of recombinant α-DG, which was required for laminin binding. We demonstrated that patients with muscle-eye-brain disease and Fukuyama congenital muscular dystrophy, as well as mice with myodystrophy, commonly have defects in a postphosphoryl modification of this phosphorylated O-linked mannose, and that this modification is mediated by the like-acetylglucosaminyltransferase (LARGE) protein. These findings expand our understanding of the mechanisms that underlie congenital muscular dystrophy.

View Full Text