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Nesprins are mechanotransducers that discriminate epithelial–mesenchymal transition programs
LINC complexes are transmembrane protein assemblies that physically connect the nucleoskeleton and cytoskeleton through the nuclear envelope. Dysfunctions of LINC complexes are associated with pathologies such as cancer and muscular disorders. The mechanical roles of LINC complexes are poorly unders...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659719/ https://www.ncbi.nlm.nih.gov/pubmed/32790861 http://dx.doi.org/10.1083/jcb.201908036 |
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author | Déjardin, Théophile Carollo, Pietro Salvatore Sipieter, François Davidson, Patricia M. Seiler, Cynthia Cuvelier, Damien Cadot, Bruno Sykes, Cecile Gomes, Edgar R. Borghi, Nicolas |
author_facet | Déjardin, Théophile Carollo, Pietro Salvatore Sipieter, François Davidson, Patricia M. Seiler, Cynthia Cuvelier, Damien Cadot, Bruno Sykes, Cecile Gomes, Edgar R. Borghi, Nicolas |
author_sort | Déjardin, Théophile |
collection | PubMed |
description | LINC complexes are transmembrane protein assemblies that physically connect the nucleoskeleton and cytoskeleton through the nuclear envelope. Dysfunctions of LINC complexes are associated with pathologies such as cancer and muscular disorders. The mechanical roles of LINC complexes are poorly understood. To address this, we used genetically encoded FRET biosensors of molecular tension in a nesprin protein of the LINC complex of fibroblastic and epithelial cells in culture. We exposed cells to mechanical, genetic, and pharmacological perturbations, mimicking a range of physiological and pathological situations. We show that nesprin experiences tension generated by the cytoskeleton and acts as a mechanical sensor of cell packing. Moreover, nesprin discriminates between inductions of partial and complete epithelial–mesenchymal transitions. We identify the implicated mechanisms, which involve α-catenin capture at the nuclear envelope by nesprin upon its relaxation, thereby regulating β-catenin transcription. Our data thus implicate LINC complex proteins as mechanotransducers that fine-tune β-catenin signaling in a manner dependent on the epithelial–mesenchymal transition program. |
format | Online Article Text |
id | pubmed-7659719 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-76597192021-04-05 Nesprins are mechanotransducers that discriminate epithelial–mesenchymal transition programs Déjardin, Théophile Carollo, Pietro Salvatore Sipieter, François Davidson, Patricia M. Seiler, Cynthia Cuvelier, Damien Cadot, Bruno Sykes, Cecile Gomes, Edgar R. Borghi, Nicolas J Cell Biol Article LINC complexes are transmembrane protein assemblies that physically connect the nucleoskeleton and cytoskeleton through the nuclear envelope. Dysfunctions of LINC complexes are associated with pathologies such as cancer and muscular disorders. The mechanical roles of LINC complexes are poorly understood. To address this, we used genetically encoded FRET biosensors of molecular tension in a nesprin protein of the LINC complex of fibroblastic and epithelial cells in culture. We exposed cells to mechanical, genetic, and pharmacological perturbations, mimicking a range of physiological and pathological situations. We show that nesprin experiences tension generated by the cytoskeleton and acts as a mechanical sensor of cell packing. Moreover, nesprin discriminates between inductions of partial and complete epithelial–mesenchymal transitions. We identify the implicated mechanisms, which involve α-catenin capture at the nuclear envelope by nesprin upon its relaxation, thereby regulating β-catenin transcription. Our data thus implicate LINC complex proteins as mechanotransducers that fine-tune β-catenin signaling in a manner dependent on the epithelial–mesenchymal transition program. Rockefeller University Press 2020-08-13 /pmc/articles/PMC7659719/ /pubmed/32790861 http://dx.doi.org/10.1083/jcb.201908036 Text en © 2020 Déjardin et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/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 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Déjardin, Théophile Carollo, Pietro Salvatore Sipieter, François Davidson, Patricia M. Seiler, Cynthia Cuvelier, Damien Cadot, Bruno Sykes, Cecile Gomes, Edgar R. Borghi, Nicolas Nesprins are mechanotransducers that discriminate epithelial–mesenchymal transition programs |
title | Nesprins are mechanotransducers that discriminate epithelial–mesenchymal transition programs |
title_full | Nesprins are mechanotransducers that discriminate epithelial–mesenchymal transition programs |
title_fullStr | Nesprins are mechanotransducers that discriminate epithelial–mesenchymal transition programs |
title_full_unstemmed | Nesprins are mechanotransducers that discriminate epithelial–mesenchymal transition programs |
title_short | Nesprins are mechanotransducers that discriminate epithelial–mesenchymal transition programs |
title_sort | nesprins are mechanotransducers that discriminate epithelial–mesenchymal transition programs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659719/ https://www.ncbi.nlm.nih.gov/pubmed/32790861 http://dx.doi.org/10.1083/jcb.201908036 |
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