Title : O-mannosyl phosphorylation of
alpha-dystroglycan is required for
laminin binding
Abstract :
- Alpha-dystroglycan ( alpha-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 alpha- 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