Syndecan-4 tunes cell mechanics by activating the kindlin-integrin-RhoA pathway.
Nat Mater
; 19(6): 669-678, 2020 06.
Article
en En
| MEDLINE
| ID: mdl-31907416
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 ß1 integrin. Tension on syndecan-4 induces cell-wide activation of the kindlin-2/ß1 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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Integrinas
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Proteína de Unión al GTP rhoA
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Mecanotransducción Celular
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Sindecano-4
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Proteínas de la Membrana
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Proteínas de Neoplasias
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nat Mater
Asunto de la revista:
CIENCIA
/
QUIMICA
Año:
2020
Tipo del documento:
Article