| Título | A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss |
|---|---|
| Autores | Servian-Morilla, Emilia , Takeuchi, Hideyuki , Lee, Tom V. , Clarimon, Jordi , Mavillard, Fabiola , Area-Gomez, Estela , Rivas, Eloy , Nieto-Gonzalez, Jose L. , Rivero, Maria C. , Cabrera-Serrano, Macarena , Gomez-Sanchez, Leonardo , MARTÍNEZ LÓPEZ, JOSÉ ANTONIO, Estrada, Beatriz , Marquez, Celedonio , Morgado, Yolanda , Suarez-Calvet, Xavier , Pita, Guillermo , Bigot, Anne , Gallardo, Eduard , Fernandez-Chacon, Rafael , Hirano, Michio , Haltiwanger, Robert S. , Jafar-Nejad, Hamed , Paradas, Carmen |
| Publicación externa | Si |
| Medio | EMBO Molecular Medicine |
| Alcance | Article |
| Naturaleza | Científica |
| Cuartil JCR | 1 |
| Cuartil SJR | 1 |
| Impacto JCR | 9.249 |
| Impacto SJR | 5.138 |
| Fecha de publicacion | 01/11/2016 |
| ISI | 000387111900005 |
| DOI | 10.15252/emmm.201505815 |
| Abstract | Skeletal muscle regeneration by muscle satellite cells is a physiological mechanism activated upon muscle damage and regulated by Notch signaling. In a family with autosomal recessive limb-girdle muscular dystrophy, we identified a missense mutation in POGLUT1 (protein O-glucosyltransferase 1), an enzyme involved in Notch posttranslational modification and function. In vitro and invivo experiments demonstrated that the mutation reduces O-glucosyltransferase activity on Notch and impairs muscle development. Muscles from patients revealed decreased Notch signaling, dramatic reduction in satellite cell pool and a muscle-specific -dystroglycan hypoglycosylation not present in patients\' fibroblasts. Primary myoblasts from patients showed slow proliferation, facilitated differentiation, and a decreased pool of quiescent PAX7(+) cells. A robust rescue of the myogenesis was demonstrated by increasing Notch signaling. None of these alterations were found in muscles from secondary dystroglycanopathy patients. These data suggest that a key pathomechanism for this novel form of muscular dystrophy is Notch-dependent loss of satellite cells. |
| Palabras clave | muscular dystrophy; Notch; O-glycosylation; POGLUT1; satellitecell |
| Miembros de la Universidad Loyola |
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