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 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.
Errataetall: |
CommentIn: Nat Mater. 2020 Jun;19(6):587-588. - PMID 32461681 |
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Medienart: |
E-Artikel |
Erscheinungsjahr: |
2020 |
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Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
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Enthalten in: |
Nature materials - 19(2020), 6 vom: 06. Juni, Seite 669-678 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Chronopoulos, Antonios [VerfasserIn] |
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Anmerkungen: |
Date Completed 24.11.2020 Date Revised 02.02.2021 published: Print-Electronic CommentIn: Nat Mater. 2020 Jun;19(6):587-588. - PMID 32461681 Citation Status MEDLINE |
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doi: |
10.1038/s41563-019-0567-1 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM305069241 |
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520 | |a 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 | ||
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700 | 1 | |a Lachowski, Dariusz |e verfasserin |4 aut | |
700 | 1 | |a Rice, Alistair J |e verfasserin |4 aut | |
700 | 1 | |a Mykuliak, Vasyl V |e verfasserin |4 aut | |
700 | 1 | |a Róg, Tomasz |e verfasserin |4 aut | |
700 | 1 | |a Lee, David A |e verfasserin |4 aut | |
700 | 1 | |a Hytönen, Vesa P |e verfasserin |4 aut | |
700 | 1 | |a Del Río Hernández, Armando E |e verfasserin |4 aut | |
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