| First Author | Yoshida-Moriguchi T | Year | 2010 |
| Journal | Science | Volume | 327 |
| Issue | 5961 | Pages | 88-92 |
| PubMed ID | 20044576 | Mgi Jnum | J:155796 |
| Mgi Id | MGI:4415738 | Doi | 10.1126/science.1180512 |
| Citation | Yoshida-Moriguchi T, et al. (2010) O-mannosyl phosphorylation of alpha-dystroglycan is required for laminin binding. Science 327(5961):88-92 |
| abstractText | 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. |
