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Syndecan-4 tunes cell mechanics by activating the kindlin-integrin-RhoA pathway

Extensive research over the past decades has identified integrins to be the primary transmembrane receptors that enable cells to respond to external mechanical cues. We reveal here a mechanism whereby syndecan-4 tunes cell mechanics in response to localised tension via a coordinated mechanochemical...

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Autores principales: Chronopoulos, Antonios, Thorpe, Stephen D., Cortes, Ernesto, Lachowski, Dariusz, Rice, Alistair J., Mykuliak, Vasyl V., Róg, Tomasz, Lee, David A., Hytönen, Vesa P., del Río Hernández, Armando E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260055/
https://www.ncbi.nlm.nih.gov/pubmed/31907416
http://dx.doi.org/10.1038/s41563-019-0567-1
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author Chronopoulos, Antonios
Thorpe, Stephen D.
Cortes, Ernesto
Lachowski, Dariusz
Rice, Alistair J.
Mykuliak, Vasyl V.
Róg, Tomasz
Lee, David A.
Hytönen, Vesa P.
del Río Hernández, Armando E.
author_facet Chronopoulos, Antonios
Thorpe, Stephen D.
Cortes, Ernesto
Lachowski, Dariusz
Rice, Alistair J.
Mykuliak, Vasyl V.
Róg, Tomasz
Lee, David A.
Hytönen, Vesa P.
del Río Hernández, Armando E.
author_sort Chronopoulos, Antonios
collection PubMed
description Extensive research over the past decades has identified integrins to be the primary transmembrane receptors that enable cells to respond to external mechanical cues. We reveal here a mechanism whereby syndecan-4 tunes cell mechanics in response to localised tension via a coordinated mechanochemical signalling response that involves activation of two other receptors: epidermal growth factor receptor, and β1 integrin. Tension on syndecan-4 induces cell-wide activation of the kindlin-2/β1 integrin/RhoA axis in a PI3K dependent manner. Furthermore, syndecan-4 mediated tension at the cell-extracellular matrix interface is required for YAP activation. Extracellular tension on syndecan-4 triggers a conformational change in the cytoplasmic domain, the variable region of which is indispensable for the mechanical adaptation to force, facilitating the assembly of a syndecan-4/α-actinin/F-actin molecular scaffold at the bead adhesion. This mechanotransduction pathway for syndecan-4 should have immediate implications for the broader field of mechanobiology.
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spelling pubmed-72600552020-07-06 Syndecan-4 tunes cell mechanics by activating the kindlin-integrin-RhoA pathway Chronopoulos, Antonios Thorpe, Stephen D. Cortes, Ernesto Lachowski, Dariusz Rice, Alistair J. Mykuliak, Vasyl V. Róg, Tomasz Lee, David A. Hytönen, Vesa P. del Río Hernández, Armando E. Nat Mater Article Extensive research over the past decades has identified integrins to be the primary transmembrane receptors that enable cells to respond to external mechanical cues. We reveal here a mechanism whereby syndecan-4 tunes cell mechanics in response to localised tension via a coordinated mechanochemical signalling response that involves activation of two other receptors: epidermal growth factor receptor, and β1 integrin. Tension on syndecan-4 induces cell-wide activation of the kindlin-2/β1 integrin/RhoA axis in a PI3K dependent manner. Furthermore, syndecan-4 mediated tension at the cell-extracellular matrix interface is required for YAP activation. Extracellular tension on syndecan-4 triggers a conformational change in the cytoplasmic domain, the variable region of which is indispensable for the mechanical adaptation to force, facilitating the assembly of a syndecan-4/α-actinin/F-actin molecular scaffold at the bead adhesion. This mechanotransduction pathway for syndecan-4 should have immediate implications for the broader field of mechanobiology. 2020-01-06 2020-06 /pmc/articles/PMC7260055/ /pubmed/31907416 http://dx.doi.org/10.1038/s41563-019-0567-1 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Chronopoulos, Antonios
Thorpe, Stephen D.
Cortes, Ernesto
Lachowski, Dariusz
Rice, Alistair J.
Mykuliak, Vasyl V.
Róg, Tomasz
Lee, David A.
Hytönen, Vesa P.
del Río Hernández, Armando E.
Syndecan-4 tunes cell mechanics by activating the kindlin-integrin-RhoA pathway
title Syndecan-4 tunes cell mechanics by activating the kindlin-integrin-RhoA pathway
title_full Syndecan-4 tunes cell mechanics by activating the kindlin-integrin-RhoA pathway
title_fullStr Syndecan-4 tunes cell mechanics by activating the kindlin-integrin-RhoA pathway
title_full_unstemmed Syndecan-4 tunes cell mechanics by activating the kindlin-integrin-RhoA pathway
title_short Syndecan-4 tunes cell mechanics by activating the kindlin-integrin-RhoA pathway
title_sort syndecan-4 tunes cell mechanics by activating the kindlin-integrin-rhoa pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260055/
https://www.ncbi.nlm.nih.gov/pubmed/31907416
http://dx.doi.org/10.1038/s41563-019-0567-1
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