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Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division
Extracellular matrix (ECM) elasticity is perceived by cells via focal adhesion structures, which transduce mechanical cues into chemical signalling to conform cell behavior. Although the contribution of ECM compliance to the control of cell migration or division is extensively studied, little is rep...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561704/ https://www.ncbi.nlm.nih.gov/pubmed/36229487 http://dx.doi.org/10.1038/s41467-022-33803-x |
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author | Petracchini, Serena Hamaoui, Daniel Doye, Anne Asnacios, Atef Fage, Florian Vitiello, Elisa Balland, Martial Janel, Sebastien Lafont, Frank Gupta, Mukund Ladoux, Benoit Gilleron, Jerôme Maia, Teresa M. Impens, Francis Gagnoux-Palacios, Laurent Daugaard, Mads Sorensen, Poul H. Lemichez, Emmanuel Mettouchi, Amel |
author_facet | Petracchini, Serena Hamaoui, Daniel Doye, Anne Asnacios, Atef Fage, Florian Vitiello, Elisa Balland, Martial Janel, Sebastien Lafont, Frank Gupta, Mukund Ladoux, Benoit Gilleron, Jerôme Maia, Teresa M. Impens, Francis Gagnoux-Palacios, Laurent Daugaard, Mads Sorensen, Poul H. Lemichez, Emmanuel Mettouchi, Amel |
author_sort | Petracchini, Serena |
collection | PubMed |
description | Extracellular matrix (ECM) elasticity is perceived by cells via focal adhesion structures, which transduce mechanical cues into chemical signalling to conform cell behavior. Although the contribution of ECM compliance to the control of cell migration or division is extensively studied, little is reported regarding infectious processes. We study this phenomenon with the extraintestinal Escherichia coli pathogen UTI89. We show that UTI89 takes advantage, via its CNF1 toxin, of integrin mechanoactivation to trigger its invasion into cells. We identify the HACE1 E3 ligase-interacting protein Optineurin (OPTN) as a protein regulated by ECM stiffness. Functional analysis establishes a role of OPTN in bacterial invasion and integrin mechanical coupling and for stimulation of HACE1 E3 ligase activity towards the Rac1 GTPase. Consistent with a role of OPTN in cell mechanics, OPTN knockdown cells display defective integrin-mediated traction force buildup, associated with limited cellular invasion by UTI89. Nevertheless, OPTN knockdown cells display strong mechanochemical adhesion signalling, enhanced Rac1 activation and increased cyclin D1 translation, together with enhanced cell proliferation independent of ECM stiffness. Together, our data ascribe a new function to OPTN in mechanobiology. |
format | Online Article Text |
id | pubmed-9561704 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95617042022-10-15 Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division Petracchini, Serena Hamaoui, Daniel Doye, Anne Asnacios, Atef Fage, Florian Vitiello, Elisa Balland, Martial Janel, Sebastien Lafont, Frank Gupta, Mukund Ladoux, Benoit Gilleron, Jerôme Maia, Teresa M. Impens, Francis Gagnoux-Palacios, Laurent Daugaard, Mads Sorensen, Poul H. Lemichez, Emmanuel Mettouchi, Amel Nat Commun Article Extracellular matrix (ECM) elasticity is perceived by cells via focal adhesion structures, which transduce mechanical cues into chemical signalling to conform cell behavior. Although the contribution of ECM compliance to the control of cell migration or division is extensively studied, little is reported regarding infectious processes. We study this phenomenon with the extraintestinal Escherichia coli pathogen UTI89. We show that UTI89 takes advantage, via its CNF1 toxin, of integrin mechanoactivation to trigger its invasion into cells. We identify the HACE1 E3 ligase-interacting protein Optineurin (OPTN) as a protein regulated by ECM stiffness. Functional analysis establishes a role of OPTN in bacterial invasion and integrin mechanical coupling and for stimulation of HACE1 E3 ligase activity towards the Rac1 GTPase. Consistent with a role of OPTN in cell mechanics, OPTN knockdown cells display defective integrin-mediated traction force buildup, associated with limited cellular invasion by UTI89. Nevertheless, OPTN knockdown cells display strong mechanochemical adhesion signalling, enhanced Rac1 activation and increased cyclin D1 translation, together with enhanced cell proliferation independent of ECM stiffness. Together, our data ascribe a new function to OPTN in mechanobiology. Nature Publishing Group UK 2022-10-13 /pmc/articles/PMC9561704/ /pubmed/36229487 http://dx.doi.org/10.1038/s41467-022-33803-x Text en © The Author(s) 2022 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 Petracchini, Serena Hamaoui, Daniel Doye, Anne Asnacios, Atef Fage, Florian Vitiello, Elisa Balland, Martial Janel, Sebastien Lafont, Frank Gupta, Mukund Ladoux, Benoit Gilleron, Jerôme Maia, Teresa M. Impens, Francis Gagnoux-Palacios, Laurent Daugaard, Mads Sorensen, Poul H. Lemichez, Emmanuel Mettouchi, Amel Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division |
title | Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division |
title_full | Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division |
title_fullStr | Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division |
title_full_unstemmed | Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division |
title_short | Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division |
title_sort | optineurin links hace1-dependent rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561704/ https://www.ncbi.nlm.nih.gov/pubmed/36229487 http://dx.doi.org/10.1038/s41467-022-33803-x |
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