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

publication date

  • June 2020

start page

  • 669

end page

  • 678

volume

  • 19

International Standard Serial Number (ISSN)

  • 1476-1122

Electronic International Standard Serial Number (EISSN)

  • 1476-4660

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.

subjects

  • Biology and Biomedicine

keywords

  • biophysical methods; computational biophysics; focal adhesion; mechanotransduction; molecular conformation