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oai:recercat.cat:2072/4273592026-03-30T04:03:31Zcom_2072_98col_2072_378192

urn:hdl:2072/427359 A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss Servián Morilla, Emilia Takeuchi, Hideyuki Lee, Tom V. Clarimón, Jordi Mavillard, Fabiola Area Gómez, Estela Rivas, Eloy Nieto González, José L. Rivero, María C. Cabrera-Serrano, Macarena Gómez Sánchez, Leonardo Martínez López, José A. Estrada, Beatriz Márquez, 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 Universitat Autònoma de Barcelona Muscular dystrophy Notch O -glycosylation Satellite cell Development & Differentiation Musculoskeletal System 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. 2016 Article 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 EMBO Molecular Medicine ; Vol. 8, Issue 11 (November 2016), p. 1289-1309 open access 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. https://creativecommons.org/licenses/by/4.0/