Characterisation of stromal-cellular mechanotransduction through syndecan-4

Research output: Contribution to conferencePosterResearch

Documents

  • FECTS 2010

    Submitted manuscript, 1 MB, PDF-document

Peter Hollosi, Alberto Grossi, John Robert Couchman

Abstract

Interaction of adherent cells with the surrounding matrix is a prerequisite for tissue homeostasis. Detailed understanding of the molecular composition, dynamics of assembly and disassembly of such site is therefore important. Focaladhesions are macromolecular assemblies present in most mammalian cell types, where mechanical forces and regulatory signals are transmitted in both directions through the plasma membrane. A cell surface heparansulphate proteoglycan, syndecan4, is a transmembrane component of focaladhesions along within tegrins, where it serves as a direct physical link between a number of extracellular matrix proteins and actinmicrofilaments. Syndecan4 knockout mice have delayed healing of skin wounds and impaired granulation tissue angiogenesis. Cells null for syndecan4 are characterised by decreased cell motility and distinct changes in their cytoskeleton, including a lack of a-smooth muscle actin in stressfibres and disorganised aactinin. Unlike in wildtype cells, detergent extraction of living null cells removes most a-actinin, an indicator of distinctly different organisation. We have shown that syndecan-4 binds a-actinin directly and now provide evidence that syndecan-4 in focal adhesions triggers a-actinin to relocate to those cell-matrix adhesion sites. This allows tension to be transmitted across the plasma membrane, shown by F-actin bundling with a-smooth muscle actin positivity. Re-introduction of syndecan-4 to null cells restores normal cytoskeleton phenotype and rate of cell migration. We map the binding site for syndecan-4 cytoplasmic domain in a-actinin to spectrin repeat4, utilising solid phase binding assays and recombinant peptides. Moreover, phosphorylation of syndecan-4 on its sole serine residue, known to influence cytoplasmic domain conformation, has no effect on a-actinin binding. In summary, syndecan-4 could be a transducer of mechanical forces in tissues through direct linkage to micro filaments.
Original languageEnglish
Publication date2010
Publication statusPublished - 2010
EventFECTS meeting -
Duration: 20 Oct 2010 → …

Conference

ConferenceFECTS meeting
Period20/10/2010 → …

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