Journal
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume 44, Issue 12, Pages 2161-2174Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2012.08.017
Keywords
Microfilaments; Focal adhesions; Adherens junctions; Proteoglycan; Heparan sulphate
Categories
Funding
- The Danish National Research Foundation
- Danish Medical Research Council
- Lundbeck Fonden
- Fabrikant Vilhelm Pedersen og Hustrus Legat through Novo Nordisk Fonden
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All cells of the musculoskeletal system possess transmembrane syndecan proteoglycans, notably syndecan-4. In fibroblasts it regulates integrin-mediated adhesion to the extracellular matrix. Syndecan-4 null mice have a complex wound repair phenotype while their fibroblasts have reduced focal adhesions and matrix contraction abilities. Signalling through syndecan-4 core protein to the actin cytoskeleton involves protein kinase C alpha and Rho family G proteins but also direct interactions with alpha-actinin. The contribution of the latter interaction to cell-matrix adhesion is not defined but investigated here since manipulation of Rho GTPase and its downstream targets could not restore a wild type microfilament organisation to syndecan-4 null cells. Microarray and protein analysis revealed no significant alterations in mRNA or protein levels for actin- or alpha-actinin associated proteins when wild type and syndecan-4 knockout fibroblasts were compared. The binding site for syndecan-4 cytoplasmic domain was identified as spectrin repeat 4 of alpha-actinin while further experiments confirmed the importance of this interaction in stabilising cell-matrix junctions. However, alpha-actinin is also present in adherens junctions, these organelles not being disrupted in the absence of syndecan-4. Indeed, co-culture of wild type and knockout cells led to adherens junction-associated stress fibre formation in cells lacking syndecan-4, supporting the hypothesis that the proteoglycan regulates cell-matrix adhesion and its associated microfilament bundles at a post-translational level. These data provide an additional dimension to syndecan function related to tension at the cell-matrix interface, wound healing and potentially fibrosis. (c) 2012 Elsevier Ltd. All rights reserved.
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