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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...

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Autores principales: Osmanagic-Myers, Selma, Foisner, Roland
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
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
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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.
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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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