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Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression
Interactions between cells and the extracellular matrix, mediated by integrin adhesion complexes, play key roles in fundamental cellular processes, including the sensing and transduction of mechanical cues. Here, we investigate systems-level changes in the integrin adhesome in patient-derived cutane...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10036544/ https://www.ncbi.nlm.nih.gov/pubmed/36959177 http://dx.doi.org/10.1038/s41467-023-37021-x |
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author | Li Mow Chee, Frederic Beernaert, Bruno Griffith, Billie G. C. Loftus, Alexander E. P. Kumar, Yatendra Wills, Jimi C. Lee, Martin Valli, Jessica Wheeler, Ann P. Armstrong, J. Douglas Parsons, Maddy Leigh, Irene M. Proby, Charlotte M. von Kriegsheim, Alex Bickmore, Wendy A. Frame, Margaret C. Byron, Adam |
author_facet | Li Mow Chee, Frederic Beernaert, Bruno Griffith, Billie G. C. Loftus, Alexander E. P. Kumar, Yatendra Wills, Jimi C. Lee, Martin Valli, Jessica Wheeler, Ann P. Armstrong, J. Douglas Parsons, Maddy Leigh, Irene M. Proby, Charlotte M. von Kriegsheim, Alex Bickmore, Wendy A. Frame, Margaret C. Byron, Adam |
author_sort | Li Mow Chee, Frederic |
collection | PubMed |
description | Interactions between cells and the extracellular matrix, mediated by integrin adhesion complexes, play key roles in fundamental cellular processes, including the sensing and transduction of mechanical cues. Here, we investigate systems-level changes in the integrin adhesome in patient-derived cutaneous squamous cell carcinoma cells and identify the actin regulatory protein Mena as a key node in the adhesion complex network. Mena is connected within a subnetwork of actin-binding proteins to the LINC complex component nesprin-2, with which it interacts and co-localises at the nuclear envelope. Moreover, Mena potentiates the interactions of nesprin-2 with the actin cytoskeleton and the nuclear lamina. CRISPR-mediated Mena depletion causes altered nuclear morphology, reduces tyrosine phosphorylation of the nuclear membrane protein emerin and downregulates expression of the immunomodulatory gene PTX3 via the recruitment of its enhancer to the nuclear periphery. We uncover an unexpected role for Mena at the nuclear membrane, where it controls nuclear architecture, chromatin repositioning and gene expression. Our findings identify an adhesion protein that regulates gene transcription via direct signalling across the nuclear envelope. |
format | Online Article Text |
id | pubmed-10036544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-100365442023-03-25 Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression Li Mow Chee, Frederic Beernaert, Bruno Griffith, Billie G. C. Loftus, Alexander E. P. Kumar, Yatendra Wills, Jimi C. Lee, Martin Valli, Jessica Wheeler, Ann P. Armstrong, J. Douglas Parsons, Maddy Leigh, Irene M. Proby, Charlotte M. von Kriegsheim, Alex Bickmore, Wendy A. Frame, Margaret C. Byron, Adam Nat Commun Article Interactions between cells and the extracellular matrix, mediated by integrin adhesion complexes, play key roles in fundamental cellular processes, including the sensing and transduction of mechanical cues. Here, we investigate systems-level changes in the integrin adhesome in patient-derived cutaneous squamous cell carcinoma cells and identify the actin regulatory protein Mena as a key node in the adhesion complex network. Mena is connected within a subnetwork of actin-binding proteins to the LINC complex component nesprin-2, with which it interacts and co-localises at the nuclear envelope. Moreover, Mena potentiates the interactions of nesprin-2 with the actin cytoskeleton and the nuclear lamina. CRISPR-mediated Mena depletion causes altered nuclear morphology, reduces tyrosine phosphorylation of the nuclear membrane protein emerin and downregulates expression of the immunomodulatory gene PTX3 via the recruitment of its enhancer to the nuclear periphery. We uncover an unexpected role for Mena at the nuclear membrane, where it controls nuclear architecture, chromatin repositioning and gene expression. Our findings identify an adhesion protein that regulates gene transcription via direct signalling across the nuclear envelope. Nature Publishing Group UK 2023-03-23 /pmc/articles/PMC10036544/ /pubmed/36959177 http://dx.doi.org/10.1038/s41467-023-37021-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Li Mow Chee, Frederic Beernaert, Bruno Griffith, Billie G. C. Loftus, Alexander E. P. Kumar, Yatendra Wills, Jimi C. Lee, Martin Valli, Jessica Wheeler, Ann P. Armstrong, J. Douglas Parsons, Maddy Leigh, Irene M. Proby, Charlotte M. von Kriegsheim, Alex Bickmore, Wendy A. Frame, Margaret C. Byron, Adam Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression |
title | Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression |
title_full | Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression |
title_fullStr | Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression |
title_full_unstemmed | Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression |
title_short | Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression |
title_sort | mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10036544/ https://www.ncbi.nlm.nih.gov/pubmed/36959177 http://dx.doi.org/10.1038/s41467-023-37021-x |
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