| First Author | Okina E | Year | 2012 |
| Journal | Int J Biochem Cell Biol | Volume | 44 |
| Issue | 12 | Pages | 2161-74 |
| PubMed ID | 22940199 | Mgi Jnum | J:345196 |
| Mgi Id | MGI:6831393 | Doi | 10.1016/j.biocel.2012.08.017 |
| Citation | Okina E, et al. (2012) Alpha-actinin interactions with syndecan-4 are integral to fibroblast-matrix adhesion and regulate cytoskeletal architecture. Int J Biochem Cell Biol 44(12):2161-74 |
| abstractText | 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 Calpha 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. |
