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| Pàgina inicial > Articles > Articles publicats > A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss |
(Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas) (Institut d'Investigació Biomèdica Sant Pau) (Universidad de Sevilla) (Universidad Pablo de Olavide) (Centro de Investigación Biomédica en Red de Enfermedades Raras) (Sorbonne Universités) (Centro de Investigación Biomédica en Red de Enfermedades Raras) (Universidad de Sevilla) (Columbia University Medical Center) (Baylor College of Medicine) (Columbia University Medical Center)| Data: | 2016 |
| Resum: | 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 1 (protein O -glucosyltransferase 1), an enzyme involved in Notch posttranslational modification and function. In vitro and in vivo 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 α-dystroglycan hypoglycosylation not present in patients' fibroblasts. Primary myoblasts from patients showed slow proliferation, facilitated differentiation, and a decreased pool of quiescent 7 + 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. |
| Ajuts: | Instituto de Salud Carlos III PI10/02410 Instituto de Salud Carlos III PI13-01739 Instituto de Salud Carlos III BA12-00097 Instituto de Salud Carlos III FIS12/2291 |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Muscular dystrophy ; Notch ; O -glycosylation ; Satellite cell ; Development & Differentiation ; Musculoskeletal System |
| Publicat a: | EMBO Molecular Medicine, Vol. 8, Issue 11 (November 2016) , p. 1289-1309, ISSN 1757-4684 |
