論文 - 詳細
| RRC ID | 43647 |
|---|---|
| 著者 | Kuga A, Kanagawa M, Sudo A, Chan YM, Tajiri M, Manya H, Kikkawa Y, Nomizu M, Kobayashi K, Endo T, Lu QL, Wada Y, Toda T. |
| タイトル | Absence of post-phosphoryl modification in dystroglycanopathy mouse models and wild-type tissues expressing non-laminin binding form of α-dystroglycan. |
| ジャーナル | J Biol Chem |
| Abstract |
α-Dystroglycan (α-DG) is a membrane-associated glycoprotein that interacts with several extracellular matrix proteins, including laminin and agrin. Aberrant glycosylation of α-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-α2,3-Gal-β1,4-GlcNAc-β1,2-Man) and a phosphodiester-linked modification on O-mannose play important roles in the laminin binding activity of α-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 α-DG. Furthermore, we have found that the glycosylation status of α-DG in lung and testis is minimally affected by defects in fukutin, LARGE, or FKRP. α-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 α-DG functional expression as a laminin receptor in normal tissues and cells. |
| 巻・号 | 287(12) |
| ページ | 9560-7 |
| 公開日 | 2012-3-16 |
| DOI | 10.1074/jbc.M111.271767 |
| PII | S0021-9258(20)60920-6 |
| PMID | 22270369 |
| PMC | PMC3308745 |
| MeSH | Animals Disease Models, Animal Dystroglycans / genetics Dystroglycans / metabolism* Female Humans Laminin / genetics Laminin / metabolism* Lung / metabolism Male Mice Mice, Transgenic Muscular Dystrophies / genetics Muscular Dystrophies / metabolism* Pentosyltransferases Phosphorylation Protein Binding Protein Processing, Post-Translational Proteins / genetics Proteins / metabolism Testis / metabolism Transferases |
| IF | 4.238 |
| 引用数 | 24 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | CHL(RCB0097) |