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Alpha-actinin interactions with syndecan-4 are integral to fibroblast-matrix adhesion and regulate cytoskeletal architecture.
Int J Biochem Cell Biol. 2012 Dec; 44(12):2161-74.IJ

Abstract

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 Cα and Rho family G proteins but also direct interactions with α-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 α-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 α-actinin while further experiments confirmed the importance of this interaction in stabilising cell-matrix junctions. However, α-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.

Authors+Show Affiliations

Department of Biomedical Sciences, University of Copenhagen, Denmark.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22940199

Citation

Okina, E, et al. "Alpha-actinin Interactions With Syndecan-4 Are Integral to Fibroblast-matrix Adhesion and Regulate Cytoskeletal Architecture." The International Journal of Biochemistry & Cell Biology, vol. 44, no. 12, 2012, pp. 2161-74.
Okina E, Grossi A, Gopal S, et al. Alpha-actinin interactions with syndecan-4 are integral to fibroblast-matrix adhesion and regulate cytoskeletal architecture. Int J Biochem Cell Biol. 2012;44(12):2161-74.
Okina, E., Grossi, A., Gopal, S., Multhaupt, H. A., & Couchman, J. R. (2012). Alpha-actinin interactions with syndecan-4 are integral to fibroblast-matrix adhesion and regulate cytoskeletal architecture. The International Journal of Biochemistry & Cell Biology, 44(12), 2161-74. https://doi.org/10.1016/j.biocel.2012.08.017
Okina E, et al. Alpha-actinin Interactions With Syndecan-4 Are Integral to Fibroblast-matrix Adhesion and Regulate Cytoskeletal Architecture. Int J Biochem Cell Biol. 2012;44(12):2161-74. PubMed PMID: 22940199.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alpha-actinin interactions with syndecan-4 are integral to fibroblast-matrix adhesion and regulate cytoskeletal architecture. AU - Okina,E, AU - Grossi,A, AU - Gopal,S, AU - Multhaupt,H A B, AU - Couchman,J R, Y1 - 2012/08/23/ PY - 2012/04/26/received PY - 2012/08/01/revised PY - 2012/08/15/accepted PY - 2012/9/4/entrez PY - 2012/9/4/pubmed PY - 2013/4/23/medline SP - 2161 EP - 74 JF - The international journal of biochemistry & cell biology JO - Int J Biochem Cell Biol VL - 44 IS - 12 N2 - 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 Cα and Rho family G proteins but also direct interactions with α-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 α-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 α-actinin while further experiments confirmed the importance of this interaction in stabilising cell-matrix junctions. However, α-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. SN - 1878-5875 UR - https://www.unboundmedicine.com/medline/citation/22940199/Alpha_actinin_interactions_with_syndecan_4_are_integral_to_fibroblast_matrix_adhesion_and_regulate_cytoskeletal_architecture_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1357-2725(12)00295-6 DB - PRIME DP - Unbound Medicine ER -