| RRC ID |
43647
|
| Author |
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.
|
| Title |
Absence of post-phosphoryl modification in dystroglycanopathy mouse models and wild-type tissues expressing non-laminin binding form of α-dystroglycan.
|
| Journal |
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.
|
| Volume |
287(12)
|
| Pages |
9560-7
|
| Published |
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
|
| Times Cited |
24
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
|
