Alpha-actinin interactions with syndecan-4 are integral to fibroblast-matrix adhesion and regulate cytoskeletal architecture
(2012) In International Journal of Biochemistry and Cell Biology 44(12). p.2161-2174- 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... (More)
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.
(Less)
- author
- Okina, E ; Grossi, A ; Gopal, S LU ; Multhaupt, H A B and Couchman, J R
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- keywords
- Actinin/chemistry, Animals, Biomechanical Phenomena, Cell Adhesion, Cells, Cultured, Extracellular Matrix/metabolism, Fibroblasts/metabolism, Focal Adhesions/metabolism, Mice, Mice, Knockout, Models, Molecular, Protein Binding, Protein Interaction Domains and Motifs, Protein Multimerization, Protein Transport, Stress Fibers/metabolism, Syndecan-4/chemistry, rho GTP-Binding Proteins/metabolism
- in
- International Journal of Biochemistry and Cell Biology
- volume
- 44
- issue
- 12
- pages
- 2161 - 2174
- publisher
- Elsevier
- external identifiers
-
- pmid:22940199
- scopus:84866522773
- ISSN
- 1878-5875
- DOI
- 10.1016/j.biocel.2012.08.017
- language
- English
- LU publication?
- no
- additional info
- Copyright © 2012 Elsevier Ltd. All rights reserved.
- id
- 4f90b8f6-e47d-42e8-869c-25784ec338c9
- date added to LUP
- 2021-10-25 13:38:27
- date last changed
- 2024-09-23 03:54:06
@article{4f90b8f6-e47d-42e8-869c-25784ec338c9, abstract = {{<p>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.</p>}}, author = {{Okina, E and Grossi, A and Gopal, S and Multhaupt, H A B and Couchman, J R}}, issn = {{1878-5875}}, keywords = {{Actinin/chemistry; Animals; Biomechanical Phenomena; Cell Adhesion; Cells, Cultured; Extracellular Matrix/metabolism; Fibroblasts/metabolism; Focal Adhesions/metabolism; Mice; Mice, Knockout; Models, Molecular; Protein Binding; Protein Interaction Domains and Motifs; Protein Multimerization; Protein Transport; Stress Fibers/metabolism; Syndecan-4/chemistry; rho GTP-Binding Proteins/metabolism}}, language = {{eng}}, number = {{12}}, pages = {{2161--2174}}, publisher = {{Elsevier}}, series = {{International Journal of Biochemistry and Cell Biology}}, title = {{Alpha-actinin interactions with syndecan-4 are integral to fibroblast-matrix adhesion and regulate cytoskeletal architecture}}, url = {{http://dx.doi.org/10.1016/j.biocel.2012.08.017}}, doi = {{10.1016/j.biocel.2012.08.017}}, volume = {{44}}, year = {{2012}}, }