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

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http://hdl.handle.net/10138/329024

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Chronopoulos , A , Thorpe , S D , Cortes , E , Lachowski , D , Rice , A J , Mykuliak , V V , Rog , T , Lee , D A , Hytönen , V P & Hernandez , A E D R 2020 , ' Syndecan-4 tunes cell mechanics by activating the kindlin-integrin-RhoA pathway ' , Nature Materials , vol. 19 , no. 6 , pp. 669-678+ . https://doi.org/10.1038/s41563-019-0567-1

Title: Syndecan-4 tunes cell mechanics by activating the kindlin-integrin-RhoA pathway
Author: Chronopoulos, Antonios; Thorpe, Stephen D.; Cortes, Ernesto; Lachowski, Dariusz; Rice, Alistair J.; Mykuliak, Vasyl V.; Rog, Tomasz; Lee, David A.; Hytönen, Vesa P.; Hernandez, Armando E. del Rio
Contributor organization: Department of Physics
Date: 2020-06
Language: eng
Number of pages: 15
Belongs to series: Nature Materials
ISSN: 1476-1122
DOI: https://doi.org/10.1038/s41563-019-0567-1
URI: http://hdl.handle.net/10138/329024
Abstract: A mechanism of cell response to localized tension shows that syndecan-4 synergizes with EGFR to elicit a mechanosignalling cascade that leads to adaptive cell stiffening through PI3K/kindlin-2 mediated integrin activation. 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 localized tension via a coordinated mechanochemical signalling response that involves activation of two other receptors: epidermal growth factor receptor and beta 1 integrin. Tension on syndecan-4 induces cell-wide activation of the kindlin-2/beta 1 integrin/RhoA axis in a PI3K-dependent manner. Furthermore, syndecan-4-mediated tension at the cell-extracellular matrix interface is required for yes-associated protein 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/alpha-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.
Subject: HEPARAN-SULFATE PROTEOGLYCANS
EPIDERMAL-GROWTH-FACTOR
MOLECULAR-DYNAMICS
ALPHA-ACTININ
PKC-ALPHA
FOCAL ADHESIONS
FORCE
MIGRATION
RECEPTOR
BINDING
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: unspecified
Usage restriction: openAccess
Self-archived version: acceptedVersion


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