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The structural and gene expression hypotheses in laminopathic diseases—not so different after all
Laminopathies are a diverse group of rare diseases with various pathologies in different tissues, which are linked to mutations in the LMNA gene. Historically, the structural disease model proposed mechanical defects of the lamina and nuclear fragility, the gene expression model impairment of spatia...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727745/ https://www.ncbi.nlm.nih.gov/pubmed/31306095 http://dx.doi.org/10.1091/mbc.E18-10-0672 |
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author | Osmanagic-Myers, Selma Foisner, Roland |
author_facet | Osmanagic-Myers, Selma Foisner, Roland |
author_sort | Osmanagic-Myers, Selma |
collection | PubMed |
description | Laminopathies are a diverse group of rare diseases with various pathologies in different tissues, which are linked to mutations in the LMNA gene. Historically, the structural disease model proposed mechanical defects of the lamina and nuclear fragility, the gene expression model impairment of spatial chromatin organization and signaling pathways as underlying mechanisms leading to the pathologies. Exciting findings in the past few years showing that mechanical forces are directly transmitted into the nucleus, where they affect chromatin organization and mechanoresponsive signaling molecules, have led to a revised concept of an integrative unified disease model, in which lamin-mediated pathways in mechanotransduction and chromatin regulation are highly interconnected and mutually dependent. In this Perspective we highlight breakthrough findings providing new insight into lamin-linked mechanisms of mechanotransduction and chromatin regulation and discuss how a combined and interrelated impairment of these functions by LMNA mutations may impair the complex mechanosignaling network and cause tissue-specific pathologies in laminopathies. |
format | Online Article Text |
id | pubmed-6727745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-67277452019-09-30 The structural and gene expression hypotheses in laminopathic diseases—not so different after all Osmanagic-Myers, Selma Foisner, Roland Mol Biol Cell Perspectives Laminopathies are a diverse group of rare diseases with various pathologies in different tissues, which are linked to mutations in the LMNA gene. Historically, the structural disease model proposed mechanical defects of the lamina and nuclear fragility, the gene expression model impairment of spatial chromatin organization and signaling pathways as underlying mechanisms leading to the pathologies. Exciting findings in the past few years showing that mechanical forces are directly transmitted into the nucleus, where they affect chromatin organization and mechanoresponsive signaling molecules, have led to a revised concept of an integrative unified disease model, in which lamin-mediated pathways in mechanotransduction and chromatin regulation are highly interconnected and mutually dependent. In this Perspective we highlight breakthrough findings providing new insight into lamin-linked mechanisms of mechanotransduction and chromatin regulation and discuss how a combined and interrelated impairment of these functions by LMNA mutations may impair the complex mechanosignaling network and cause tissue-specific pathologies in laminopathies. The American Society for Cell Biology 2019-07-15 /pmc/articles/PMC6727745/ /pubmed/31306095 http://dx.doi.org/10.1091/mbc.E18-10-0672 Text en © 2019 Osmanagic-Myers and Foisner. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Perspectives Osmanagic-Myers, Selma Foisner, Roland The structural and gene expression hypotheses in laminopathic diseases—not so different after all |
title | The structural and gene expression hypotheses in laminopathic diseases—not so different after all |
title_full | The structural and gene expression hypotheses in laminopathic diseases—not so different after all |
title_fullStr | The structural and gene expression hypotheses in laminopathic diseases—not so different after all |
title_full_unstemmed | The structural and gene expression hypotheses in laminopathic diseases—not so different after all |
title_short | The structural and gene expression hypotheses in laminopathic diseases—not so different after all |
title_sort | structural and gene expression hypotheses in laminopathic diseases—not so different after all |
topic | Perspectives |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727745/ https://www.ncbi.nlm.nih.gov/pubmed/31306095 http://dx.doi.org/10.1091/mbc.E18-10-0672 |
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