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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...

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Autores principales: Méjat, Alexandre, Decostre, Valérie, Li, Juan, Renou, Laure, Kesari, Akanchha, Hantaï, Daniel, Stewart, Colin L., Xiao, Xiao, Hoffman, Eric, Bonne, Gisèle, Misteli, Tom
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
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.
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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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