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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...

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Autores principales: Déjardin, Théophile, Carollo, Pietro Salvatore, Sipieter, François, Davidson, Patricia M., Seiler, Cynthia, Cuvelier, Damien, Cadot, Bruno, Sykes, Cecile, Gomes, Edgar R., Borghi, Nicolas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
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.
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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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