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Lamin A/C–mediated neuromuscular junction defects in Emery-Dreifuss muscular dystrophy
The LMNA gene encodes lamins A and C, two intermediate filament-type proteins that are important determinants of interphase nuclear architecture. Mutations in LMNA lead to a wide spectrum of human diseases including autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD), which affects skelet...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615092/ https://www.ncbi.nlm.nih.gov/pubmed/19124654 http://dx.doi.org/10.1083/jcb.200811035 |
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author | Méjat, Alexandre Decostre, Valérie Li, Juan Renou, Laure Kesari, Akanchha Hantaï, Daniel Stewart, Colin L. Xiao, Xiao Hoffman, Eric Bonne, Gisèle Misteli, Tom |
author_facet | Méjat, Alexandre Decostre, Valérie Li, Juan Renou, Laure Kesari, Akanchha Hantaï, Daniel Stewart, Colin L. Xiao, Xiao Hoffman, Eric Bonne, Gisèle Misteli, Tom |
author_sort | Méjat, Alexandre |
collection | PubMed |
description | The LMNA gene encodes lamins A and C, two intermediate filament-type proteins that are important determinants of interphase nuclear architecture. Mutations in LMNA lead to a wide spectrum of human diseases including autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD), which affects skeletal and cardiac muscle. The cellular mechanisms by which mutations in LMNA cause disease have been elusive. Here, we demonstrate that defects in neuromuscular junctions (NMJs) are part of the disease mechanism in AD-EDMD. Two AD-EDMD mouse models show innervation defects including misexpression of electrical activity–dependent genes and altered epigenetic chromatin modifications. Synaptic nuclei are not properly recruited to the NMJ because of mislocalization of nuclear envelope components. AD-EDMD patients with LMNA mutations show the same cellular defects as the AD-EDMD mouse models. These results suggest that lamin A/C–mediated NMJ defects contribute to the AD-EDMD disease phenotype and provide insights into the cellular and molecular mechanisms for the muscle-specific phenotype of AD-EDMD. |
format | Text |
id | pubmed-2615092 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-26150922009-07-12 Lamin A/C–mediated neuromuscular junction defects in Emery-Dreifuss muscular dystrophy Méjat, Alexandre Decostre, Valérie Li, Juan Renou, Laure Kesari, Akanchha Hantaï, Daniel Stewart, Colin L. Xiao, Xiao Hoffman, Eric Bonne, Gisèle Misteli, Tom J Cell Biol Research Articles The LMNA gene encodes lamins A and C, two intermediate filament-type proteins that are important determinants of interphase nuclear architecture. Mutations in LMNA lead to a wide spectrum of human diseases including autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD), which affects skeletal and cardiac muscle. The cellular mechanisms by which mutations in LMNA cause disease have been elusive. Here, we demonstrate that defects in neuromuscular junctions (NMJs) are part of the disease mechanism in AD-EDMD. Two AD-EDMD mouse models show innervation defects including misexpression of electrical activity–dependent genes and altered epigenetic chromatin modifications. Synaptic nuclei are not properly recruited to the NMJ because of mislocalization of nuclear envelope components. AD-EDMD patients with LMNA mutations show the same cellular defects as the AD-EDMD mouse models. These results suggest that lamin A/C–mediated NMJ defects contribute to the AD-EDMD disease phenotype and provide insights into the cellular and molecular mechanisms for the muscle-specific phenotype of AD-EDMD. The Rockefeller University Press 2009-01-12 /pmc/articles/PMC2615092/ /pubmed/19124654 http://dx.doi.org/10.1083/jcb.200811035 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Méjat, Alexandre Decostre, Valérie Li, Juan Renou, Laure Kesari, Akanchha Hantaï, Daniel Stewart, Colin L. Xiao, Xiao Hoffman, Eric Bonne, Gisèle Misteli, Tom Lamin A/C–mediated neuromuscular junction defects in Emery-Dreifuss muscular dystrophy |
title | Lamin A/C–mediated neuromuscular junction defects in Emery-Dreifuss muscular dystrophy |
title_full | Lamin A/C–mediated neuromuscular junction defects in Emery-Dreifuss muscular dystrophy |
title_fullStr | Lamin A/C–mediated neuromuscular junction defects in Emery-Dreifuss muscular dystrophy |
title_full_unstemmed | Lamin A/C–mediated neuromuscular junction defects in Emery-Dreifuss muscular dystrophy |
title_short | Lamin A/C–mediated neuromuscular junction defects in Emery-Dreifuss muscular dystrophy |
title_sort | lamin a/c–mediated neuromuscular junction defects in emery-dreifuss muscular dystrophy |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615092/ https://www.ncbi.nlm.nih.gov/pubmed/19124654 http://dx.doi.org/10.1083/jcb.200811035 |
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