Web of Science: 25 citations, Scopus: 27 citations, Google Scholar: citations,
A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss
Servián Morilla, Emilia (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED))
Takeuchi, Hideyuki (The University of Georgia)
Lee, Tom V. (Baylor College of Medicine)
Clarimon, Jordi (Institut d'Investigació Biomèdica Sant Pau)
Mavillard, Fabiola (Universidad de Sevilla)
Area Gómez, Estela (Columbia University Medical Center)
Rivas, Eloy (Universidad de Sevilla)
Nieto González, José L. (Universidad de Sevilla)
Rivero, María C. (Universidad de Sevilla)
Cabrera Serrano, Macarena (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED))
Gómez Sánchez, Leonardo (Universidad de Sevilla)
Martínez López, José A. (Universidad de Sevilla)
Estrada, Beatriz (Universidad Pablo Olavide)
Márquez, Celedonio (Universidad de Sevilla)
Morgado, Yolanda (Hospital U. Valme)
Suárez Calvet, Xavier (Centro de Investigación Biomédica en Red sobre Enfermedades Raras (CIBERER))
Pita, Guillermo (Centro Nacional de Investigaciones Oncológicas)
Bigot, Anne (Sorbonne Universités)
Gallardo Vigo, Eduard (Centro de Investigación Biomédica en Red sobre Enfermedades Raras (CIBERER))
Fernández Chacón, Rafael (Universidad de Sevilla)
Hirano, Michio (Columbia University Medical Center)
Haltiwanger, Robert S. (The University of Georgia)
Jafar‐Nejad, Hamed (Baylor College of Medicine)
Paradas, Carmen (Columbia University Medical Center)
Universitat Autònoma de Barcelona

Date: 2016
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 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.
Note: Número d'acord de subvenció ISCIII/PI10/02410
Note: Número d'acord de subvenció ISCIII/PI13-01739
Note: Número d'acord de subvenció ISCIII/BA12-00097
Note: Número d'acord de subvenció ISCIII/FIS12/2291
Rights: 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. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Muscular dystrophy ; Notch ; O ‐glycosylation ; Satellite cell ; Development & Differentiation ; Musculoskeletal System
Published in: EMBO Molecular Medicine, Vol. 8, Issue 11 (November 2016) , p. 1289-1309, ISSN 1757-4684

PMID: 27807076
DOI: 10.15252/emmm.201505815


21 p, 4.8 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació Biomèdica Sant Pau
Articles > Research articles
Articles > Published articles

 Record created 2018-02-07, last modified 2019-04-11



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