| First Author | Yagi H | Year | 2013 |
| Journal | Sci Rep | Volume | 3 |
| Pages | 3288 | PubMed ID | 24256719 |
| Mgi Jnum | J:215959 | Mgi Id | MGI:5607394 |
| Doi | 10.1038/srep03288 | Citation | Yagi H, et al. (2013) AGO61-dependent GlcNAc modification primes the formation of functional glycans on alpha-dystroglycan. Sci Rep 3:3288 |
| abstractText | Dystroglycanopathy is a major class of congenital muscular dystrophy that is caused by a deficiency of functional glycans on alpha-dystroglycan (alpha-DG) with laminin-binding activity. A product of a recently identified causative gene for dystroglycanopathy, AGO61, acted in vitro as a protein O-mannose beta-1, 4-N-acetylglucosaminyltransferase, although it was not functionally characterized. Here we show the phenotypes of AGO61-knockout mice and demonstrate that AGO61 is indispensable for the formation of laminin-binding glycans of alpha-DG. AGO61-knockout mouse brain exhibited abnormal basal lamina formation and a neuronal migration defect due to a lack of laminin-binding glycans. Furthermore, our results indicate that functional alpha-DG glycosylation was primed by AGO61-dependent GlcNAc modifications of specific threonine-linked mannosyl moieties of alpha-DG. These findings provide a key missing link for understanding how the physiologically critical glycan motif is displayed on alpha-DG and provides new insights on the pathological mechanisms of dystroglycanopathy. |
