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A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss
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 e...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5090660/ https://www.ncbi.nlm.nih.gov/pubmed/27807076 http://dx.doi.org/10.15252/emmm.201505815 |
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author | Servián‐Morilla, Emilia Takeuchi, Hideyuki Lee, Tom V Clarimon, Jordi Mavillard, Fabiola Area‐Gómez, Estela Rivas, Eloy Nieto‐González, Jose L Rivero, Maria C Cabrera‐Serrano, Macarena Gómez‐Sánchez, Leonardo Martínez‐López, Jose A Estrada, Beatriz Márquez, Celedonio Morgado, Yolanda Suárez‐Calvet, Xavier Pita, Guillermo Bigot, Anne Gallardo, Eduard Fernández‐Chacón, Rafael Hirano, Michio Haltiwanger, Robert S Jafar‐Nejad, Hamed Paradas, Carmen |
author_facet | Servián‐Morilla, Emilia Takeuchi, Hideyuki Lee, Tom V Clarimon, Jordi Mavillard, Fabiola Area‐Gómez, Estela Rivas, Eloy Nieto‐González, Jose L Rivero, Maria C Cabrera‐Serrano, Macarena Gómez‐Sánchez, Leonardo Martínez‐López, Jose A Estrada, Beatriz Márquez, Celedonio Morgado, Yolanda Suárez‐Calvet, Xavier Pita, Guillermo Bigot, Anne Gallardo, Eduard Fernández‐Chacón, Rafael Hirano, Michio Haltiwanger, Robert S Jafar‐Nejad, Hamed Paradas, Carmen |
author_sort | Servián‐Morilla, Emilia |
collection | PubMed |
description | 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 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 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. |
format | Online Article Text |
id | pubmed-5090660 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-50906602016-11-25 A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss Servián‐Morilla, Emilia Takeuchi, Hideyuki Lee, Tom V Clarimon, Jordi Mavillard, Fabiola Area‐Gómez, Estela Rivas, Eloy Nieto‐González, Jose L Rivero, Maria C Cabrera‐Serrano, Macarena Gómez‐Sánchez, Leonardo Martínez‐López, Jose A Estrada, Beatriz Márquez, Celedonio Morgado, Yolanda Suárez‐Calvet, Xavier Pita, Guillermo Bigot, Anne Gallardo, Eduard Fernández‐Chacón, Rafael Hirano, Michio Haltiwanger, Robert S Jafar‐Nejad, Hamed Paradas, Carmen EMBO Mol Med Research Articles 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 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 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. John Wiley and Sons Inc. 2016-10-10 2016-11 /pmc/articles/PMC5090660/ /pubmed/27807076 http://dx.doi.org/10.15252/emmm.201505815 Text en © 2016 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Servián‐Morilla, Emilia Takeuchi, Hideyuki Lee, Tom V Clarimon, Jordi Mavillard, Fabiola Area‐Gómez, Estela Rivas, Eloy Nieto‐González, Jose L Rivero, Maria C Cabrera‐Serrano, Macarena Gómez‐Sánchez, Leonardo Martínez‐López, Jose A Estrada, Beatriz Márquez, Celedonio Morgado, Yolanda Suárez‐Calvet, Xavier Pita, Guillermo Bigot, Anne Gallardo, Eduard Fernández‐Chacón, Rafael Hirano, Michio Haltiwanger, Robert S Jafar‐Nejad, Hamed Paradas, Carmen A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss |
title | A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss |
title_full | A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss |
title_fullStr | A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss |
title_full_unstemmed | A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss |
title_short | A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss |
title_sort | poglut1 mutation causes a muscular dystrophy with reduced notch signaling and satellite cell loss |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5090660/ https://www.ncbi.nlm.nih.gov/pubmed/27807076 http://dx.doi.org/10.15252/emmm.201505815 |
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