| First Author | Willer T | Year | 2014 |
| Journal | Elife | Volume | 3 |
| PubMed ID | 25279699 | Mgi Jnum | J:218034 |
| Mgi Id | MGI:5616472 | Doi | 10.7554/eLife.03941 |
| Citation | Willer T, et al. (2014) The glucuronyltransferase B4GAT1 is required for initiation of LARGE-mediated alpha-dystroglycan functional glycosylation. Elife 3 |
| abstractText | Dystroglycan is a cell membrane receptor that organizes the basement membrane by binding ligands in the extracellular matrix. Proper glycosylation of the alpha-dystroglycan (alpha-DG) subunit is essential for these activities, and lack thereof results in neuromuscular disease. Currently, neither the glycan synthesis pathway nor the roles of many known or putative glycosyltransferases that are essential for this process are well understood. Here we show that FKRP, FKTN, TMEM5 and B4GAT1 (formerly known as B3GNT1) localize to the Golgi and contribute to the O-mannosyl post-phosphorylation modification of alpha-DG. Moreover, we assigned B4GAT1 a function as a xylose beta1,4-glucuronyltransferase. Nuclear magnetic resonance studies confirmed that a glucuronic acid beta1,4-xylose disaccharide synthesized by B4GAT1 acts as an acceptor primer that can be elongated by LARGE with the ligand-binding heteropolysaccharide. Our findings greatly broaden the understanding of alpha-DG glycosylation and provide mechanistic insight into why mutations in B4GAT1 disrupt dystroglycan function and cause disease. |
