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Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells
Emery-Dreifuss muscular dystrophy can be caused by mutations in the nuclear envelope proteins lamin A/C and emerin. We recently demonstrated that A-type lamin-deficient cells have impaired nuclear mechanics and altered mechanotransduction, suggesting two potential disease mechanisms (Lammerding, J.,...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171355/ https://www.ncbi.nlm.nih.gov/pubmed/16115958 http://dx.doi.org/10.1083/jcb.200502148 |
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author | Lammerding, Jan Hsiao, Janet Schulze, P. Christian Kozlov, Serguei Stewart, Colin L. Lee, Richard T. |
author_facet | Lammerding, Jan Hsiao, Janet Schulze, P. Christian Kozlov, Serguei Stewart, Colin L. Lee, Richard T. |
author_sort | Lammerding, Jan |
collection | PubMed |
description | Emery-Dreifuss muscular dystrophy can be caused by mutations in the nuclear envelope proteins lamin A/C and emerin. We recently demonstrated that A-type lamin-deficient cells have impaired nuclear mechanics and altered mechanotransduction, suggesting two potential disease mechanisms (Lammerding, J., P.C. Schulze, T. Takahashi, S. Kozlov, T. Sullivan, R.D. Kamm, C.L. Stewart, and R.T. Lee. 2004. J. Clin. Invest. 113:370–378). Here, we examined the function of emerin on nuclear mechanics and strain-induced signaling. Emerin-deficient mouse embryo fibroblasts have abnormal nuclear shape, but in contrast to A-type lamin-deficient cells, exhibit nuclear deformations comparable to wild-type cells in cellular strain experiments, and the integrity of emerin-deficient nuclear envelopes appeared normal in a nuclear microinjection assay. Interestingly, expression of mechanosensitive genes in response to mechanical strain was impaired in emerin-deficient cells, and prolonged mechanical stimulation increased apoptosis in emerin-deficient cells. Thus, emerin-deficient mouse embryo fibroblasts have apparently normal nuclear mechanics but impaired expression of mechanosensitive genes in response to strain, suggesting that emerin mutations may act through altered transcriptional regulation and not by increasing nuclear fragility. |
format | Text |
id | pubmed-2171355 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21713552008-03-05 Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells Lammerding, Jan Hsiao, Janet Schulze, P. Christian Kozlov, Serguei Stewart, Colin L. Lee, Richard T. J Cell Biol Research Articles Emery-Dreifuss muscular dystrophy can be caused by mutations in the nuclear envelope proteins lamin A/C and emerin. We recently demonstrated that A-type lamin-deficient cells have impaired nuclear mechanics and altered mechanotransduction, suggesting two potential disease mechanisms (Lammerding, J., P.C. Schulze, T. Takahashi, S. Kozlov, T. Sullivan, R.D. Kamm, C.L. Stewart, and R.T. Lee. 2004. J. Clin. Invest. 113:370–378). Here, we examined the function of emerin on nuclear mechanics and strain-induced signaling. Emerin-deficient mouse embryo fibroblasts have abnormal nuclear shape, but in contrast to A-type lamin-deficient cells, exhibit nuclear deformations comparable to wild-type cells in cellular strain experiments, and the integrity of emerin-deficient nuclear envelopes appeared normal in a nuclear microinjection assay. Interestingly, expression of mechanosensitive genes in response to mechanical strain was impaired in emerin-deficient cells, and prolonged mechanical stimulation increased apoptosis in emerin-deficient cells. Thus, emerin-deficient mouse embryo fibroblasts have apparently normal nuclear mechanics but impaired expression of mechanosensitive genes in response to strain, suggesting that emerin mutations may act through altered transcriptional regulation and not by increasing nuclear fragility. The Rockefeller University Press 2005-08-29 /pmc/articles/PMC2171355/ /pubmed/16115958 http://dx.doi.org/10.1083/jcb.200502148 Text en Copyright © 2005, Government 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.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Lammerding, Jan Hsiao, Janet Schulze, P. Christian Kozlov, Serguei Stewart, Colin L. Lee, Richard T. Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells |
title | Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells |
title_full | Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells |
title_fullStr | Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells |
title_full_unstemmed | Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells |
title_short | Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells |
title_sort | abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171355/ https://www.ncbi.nlm.nih.gov/pubmed/16115958 http://dx.doi.org/10.1083/jcb.200502148 |
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