| First Author | Kanagawa M | Year | 2016 |
| Journal | Cell Rep | Volume | 14 |
| Issue | 9 | Pages | 2209-2223 |
| PubMed ID | 26923585 | Mgi Jnum | J:234365 |
| Mgi Id | MGI:5789846 | Doi | 10.1016/j.celrep.2016.02.017 |
| Citation | Kanagawa M, et al. (2016) Identification of a Post-translational Modification with Ribitol-Phosphate and Its Defect in Muscular Dystrophy. Cell Rep 14(9):2209-23 |
| abstractText | Glycosylation is an essential post-translational modification that underlies many biological processes and diseases. alpha-dystroglycan (alpha-DG) is a receptor for matrix and synaptic proteins that causes muscular dystrophy and lissencephaly upon its abnormal glycosylation (alpha-dystroglycanopathies). Here we identify the glycan unit ribitol 5-phosphate (Rbo5P), a phosphoric ester of pentose alcohol, in alpha-DG. Rbo5P forms a tandem repeat and functions as a scaffold for the formation of the ligand-binding moiety. We show that enzyme activities of three major alpha-dystroglycanopathy-causing proteins are involved in the synthesis of tandem Rbo5P. Isoprenoid synthase domain-containing (ISPD) is cytidine diphosphate ribitol (CDP-Rbo) synthase. Fukutin and fukutin-related protein are sequentially acting Rbo5P transferases that use CDP-Rbo. Consequently, Rbo5P glycosylation is defective in alpha-dystroglycanopathy models. Supplementation of CDP-Rbo to ISPD-deficient cells restored alpha-DG glycosylation. These findings establish the molecular basis of mammalian Rbo5P glycosylation and provide insight into pathogenesis and therapeutic strategies in alpha-DG-associated diseases. |
