| First Author | Zhang Z | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 4 | Pages | e19080 |
| PubMed ID | 21533062 | Mgi Jnum | J:172396 |
| Mgi Id | MGI:5007594 | Doi | 10.1371/journal.pone.0019080 |
| Citation | Zhang Z, et al. (2011) LARGE Expression Augments the Glycosylation of Glycoproteins in Addition to alpha-Dystroglycan Conferring Laminin Binding. PLoS One 6(4):e19080 |
| abstractText | Mutations in genes encoding glycosyltransferases (and presumed glycosyltransferases) that affect glycosylation and extracellular matrix binding activity of alpha-dystroglycan (alpha-DG) cause congenital muscular dystrophies (CMDs) with central nervous system manifestations. Among the identified genes, LARGE is of particular interest because its overexpression rescues glycosylation defects of alpha-DG in mutations of not only LARGE but also other CMD-causing genes and restores laminin binding activity of alpha-DG. It is not known whether LARGE protein glycosylates other proteins in addition to alpha-DG. In this study, we overexpressed LARGE in DG-deficient cells and analyzed glycosylated proteins by Western blot analysis. Surprisingly, overexpression of LARGE in alpha-DG-deficient cells led to glycosylation dependent IIH6C4 and VIA4-1 immunoreactivity, despite the prevailing view that these antibodies only recognize glycosylated alpha-DG. Furthermore, the hyperglycosylated proteins in LARGE-overexpressing cells demonstrated the functional capacity to bind the extracellular matrix molecule laminin and promote laminin assembly at the cell surface, an effect that was blocked by IIH6C4 antibodies. These results indicate that overexpression of LARGE catalyzes the glycosylation of at least one other glycoprotein in addition to alpha-DG, and that this glycosylation(s) promotes laminin binding activity. |
