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

Antonios Chronopoulos, Stephen D. Thorpe, Ernesto Cortes, Dariusz Lachowski, Alistair J. Rice, Vasyl V. Mykuliak, Tomasz Rog, David A. Lee, Tomasz Róg, Vesa P. Hytönen, Armando E. del Río Hernández

Research output: Contribution to journalArticleScientificpeer-review

17 Citations (Scopus)

Abstract

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 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 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/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.

Original languageEnglish
Pages (from-to)669-678
Number of pages15
JournalNature Materials
Volume19
Issue number6
DOIs
Publication statusPublished - 2020
Publication typeA1 Journal article-refereed

Publication forum classification

  • Publication forum level 3

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