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Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling

Cadherins control intercellular adhesion in most metazoans. In vertebrates, intercellular adhesion differs considerably between cadherins of type-I and type-II, predominantly due to their different extracellular regions. Yet, intercellular adhesion critically depends on actomyosin contractility, in...

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Autores principales: Aladin, Darwesh Mohideen Kaderbatcha, Chu, Yeh Shiu, Shen, Shuo, Robinson, Robert Charles, Dufour, Sylvie, Viasnoff, Virgile, Borghi, Nicolas, Thiery, Jean Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8694416/
https://www.ncbi.nlm.nih.gov/pubmed/34937057
http://dx.doi.org/10.1371/journal.pone.0260593
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author Aladin, Darwesh Mohideen Kaderbatcha
Chu, Yeh Shiu
Shen, Shuo
Robinson, Robert Charles
Dufour, Sylvie
Viasnoff, Virgile
Borghi, Nicolas
Thiery, Jean Paul
author_facet Aladin, Darwesh Mohideen Kaderbatcha
Chu, Yeh Shiu
Shen, Shuo
Robinson, Robert Charles
Dufour, Sylvie
Viasnoff, Virgile
Borghi, Nicolas
Thiery, Jean Paul
author_sort Aladin, Darwesh Mohideen Kaderbatcha
collection PubMed
description Cadherins control intercellular adhesion in most metazoans. In vertebrates, intercellular adhesion differs considerably between cadherins of type-I and type-II, predominantly due to their different extracellular regions. Yet, intercellular adhesion critically depends on actomyosin contractility, in which the role of the cadherin extracellular region is unclear. Here, we dissect the roles of the Extracellular Cadherin (EC) Ig-like domains by expressing chimeric E-cadherin with E-cadherin and cadherin-7 Ig-like domains in cells naturally devoid of cadherins. Using cell-cell separation, cortical tension measurement, tissue stretching and migration assays, we show that distinct EC repeats in the extracellular region of cadherins differentially modulate epithelial sheet integrity, cell-cell separation forces, and cell cortical tension with the Cdc42 pathway, which further differentially regulate epithelial tensile strength, ductility, and ultimately collective migration. Interestingly, dissipative processes rather than static adhesion energy mostly dominate cell-cell separation forces. We provide a framework for the emergence of epithelial phenotypes from cell mechanical properties dependent on EC outside-in signaling.
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spelling pubmed-86944162021-12-23 Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling Aladin, Darwesh Mohideen Kaderbatcha Chu, Yeh Shiu Shen, Shuo Robinson, Robert Charles Dufour, Sylvie Viasnoff, Virgile Borghi, Nicolas Thiery, Jean Paul PLoS One Research Article Cadherins control intercellular adhesion in most metazoans. In vertebrates, intercellular adhesion differs considerably between cadherins of type-I and type-II, predominantly due to their different extracellular regions. Yet, intercellular adhesion critically depends on actomyosin contractility, in which the role of the cadherin extracellular region is unclear. Here, we dissect the roles of the Extracellular Cadherin (EC) Ig-like domains by expressing chimeric E-cadherin with E-cadherin and cadherin-7 Ig-like domains in cells naturally devoid of cadherins. Using cell-cell separation, cortical tension measurement, tissue stretching and migration assays, we show that distinct EC repeats in the extracellular region of cadherins differentially modulate epithelial sheet integrity, cell-cell separation forces, and cell cortical tension with the Cdc42 pathway, which further differentially regulate epithelial tensile strength, ductility, and ultimately collective migration. Interestingly, dissipative processes rather than static adhesion energy mostly dominate cell-cell separation forces. We provide a framework for the emergence of epithelial phenotypes from cell mechanical properties dependent on EC outside-in signaling. Public Library of Science 2021-12-22 /pmc/articles/PMC8694416/ /pubmed/34937057 http://dx.doi.org/10.1371/journal.pone.0260593 Text en © 2021 Aladin et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Aladin, Darwesh Mohideen Kaderbatcha
Chu, Yeh Shiu
Shen, Shuo
Robinson, Robert Charles
Dufour, Sylvie
Viasnoff, Virgile
Borghi, Nicolas
Thiery, Jean Paul
Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling
title Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling
title_full Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling
title_fullStr Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling
title_full_unstemmed Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling
title_short Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling
title_sort extracellular domains of e-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8694416/
https://www.ncbi.nlm.nih.gov/pubmed/34937057
http://dx.doi.org/10.1371/journal.pone.0260593
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