| First Author | Kuga A | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 12 | Pages | 9560-7 |
| PubMed ID | 22270369 | Mgi Jnum | J:183288 |
| Mgi Id | MGI:5318171 | Doi | 10.1074/jbc.M111.271767 |
| Citation | Kuga A, et al. (2012) Absence of post-phosphoryl modification in dystroglycanopathy mouse models and wild-type tissues expressing non-laminin binding form of alpha-dystroglycan. J Biol Chem 287(12):9560-7 |
| abstractText | alpha-Dystroglycan (alpha-DG) is a membrane-associated glycoprotein that interacts with several extracellular matrix proteins, including laminin and agrin. Aberrant glycosylation of alpha-DG disrupts its interaction with ligands and causes a certain type of muscular dystrophy commonly referred to as dystroglycanopathy. It has been reported that a unique O-mannosyl tetrasaccharide (Neu5Ac-alpha2,3-Gal-beta1,4-GlcNAc-beta1,2-Man) and a phosphodiester-linked modification on O-mannose play important roles in the laminin binding activity of alpha-DG. In this study, we use several dystroglycanopathy mouse models to demonstrate that, in addition to fukutin and LARGE, FKRP (fukutin-related protein) is also involved in the post-phosphoryl modification of O-mannose on alpha-DG. Furthermore, we have found that the glycosylation status of alpha-DG in lung and testis is minimally affected by defects in fukutin, LARGE, or FKRP. alpha-DG prepared from wild-type lung- or testis-derived cells lacks the post-phosphoryl moiety and shows little laminin-binding activity. These results show that FKRP is involved in post-phosphoryl modification rather than in O-mannosyl tetrasaccharide synthesis. Our data also demonstrate that post-phosphoryl modification not only plays critical roles in the pathogenesis of dystroglycanopathy but also is a key determinant of alpha-DG functional expression as a laminin receptor in normal tissues and cells. |
