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

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 ?1 integrin. Tension on syndecan-4 induces cell-wide activation of the kindlin-2/?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/?-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.

SUBMITTER: Chronopoulos A 

PROVIDER: S-EPMC7260055 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature