| First Author | Kanagawa M | Year | 2004 |
| Journal | Cell | Volume | 117 |
| Issue | 7 | Pages | 953-64 |
| PubMed ID | 15210115 | Mgi Jnum | J:175194 |
| Mgi Id | MGI:5284802 | Doi | 10.1016/j.cell.2004.06.003 |
| Citation | Kanagawa M, et al. (2004) Molecular recognition by LARGE is essential for expression of functional dystroglycan. Cell 117(7):953-64 |
| abstractText | Reduced ligand binding activity of alpha-dystroglycan is associated with muscle and central nervous system pathogenesis in a growing number of muscular dystrophies. Posttranslational processing of alpha-dystroglycan is generally accepted to be critical for the expression of functional dystroglycan. Here we show that both the N-terminal domain and a portion of the mucin-like domain of alpha-dystroglycan are essential for high-affinity laminin-receptor function. Posttranslational modification of alpha-dystroglycan by glycosyltransferase, LARGE, occurs within the mucin-like domain, but the N-terminal domain interacts with LARGE, defining an intracellular enzyme-substrate recognition motif necessary to initiate functional glycosylation. Gene replacement in dystroglycan-deficient muscle demonstrates that the dystroglycan C-terminal domain is sufficient only for dystrophin-glycoprotein complex assembly, but to prevent muscle degeneration the expression of a functional dystroglycan through LARGE recognition and glycosylation is required. Therefore, molecular recognition of dystroglycan by LARGE is a key determinant in the biosynthetic pathway to produce mature and functional dystroglycan. |
