ArticleCell communication and signaling : CCS2020
Syndecan-4/PAR-3 signaling regulates focal adhesion dynamics in mesenchymal cells.
Article in Cell communication and signaling : CCS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Homing and Migration of Umbilical Cord Mesenchymal Stromal Cells in Clinical Applications: Molecular Mechanisms, Translational Barriers, and Therapeutic Optimization.Stem cell reviews and reports · 2026Review
- Human tissue kallikrein 14 induces the expression of IL-6, IL-8, and CXCL1 in skin fibroblasts through protease-activated receptor 1 signaling.The FEBS journal · 2025Article
- Serum proteome profiling of plateau acclimatization in men using Olink proteomics approach.Physiological reports · 2024Article
- A Pro-Inflammatory Stimulus versus Extensive Passaging of DITNC1 Astrocyte Cultures as Models to Study Astrogliosis.International journal of molecular sciences · 2024Article
- The molecular determinants of microglial developmental dynamics.Nature reviews. Neuroscience · 2024Review
- Protein kinase B (AKT) upregulation and Thy-1-αJournal of neuroinflammation · 2023Article
- Nox1-based NADPH oxidase regulates the Par protein complex activity to control cell polarization.Frontiers in cell and developmental biology · 2023Article
- Thy-1 (CD90)-regulated cell adhesion and migration of mesenchymal cells: insights into adhesomes, mechanical forces, and signaling pathways.Frontiers in cell and developmental biology · 2023Review
- Editorial: In celebration of women in cell adhesion and migration.Frontiers in cell and developmental biology · 2023Article
- A reduction of Syndecan-4 in macrophages promotes atherosclerosis by aggravating the proinflammatory capacity of macrophages.Journal of translational medicine · 2022Article
- CK2β Is a Gatekeeper of Focal Adhesions Regulating Cell Spreading.Frontiers in molecular biosciences · 2022Article
- Thy-1-Integrin Interactions inFrontiers in cell and developmental biology · 2022Review
- Thy-1 (CD90), Integrins and Syndecan 4 are Key Regulators of Skin Wound Healing.Frontiers in cell and developmental biology · 2022Review
- Syndecan-4 as a Pathogenesis Factor and Therapeutic Target in Cancer.Biomolecules · 2021Review
- Development of a library of laminin-mimetic peptide hydrogels for control of nucleus pulposus cell behaviors.Journal of tissue engineeringArticle
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundSyndecans regulate cell migration thus having key roles in scarring and wound healing processes. Our previous results have shown that Thy-1/CD90 can engage both αvβ3 integrin and Syndecan-4 expressed on the surface of astrocytes to induce cell migration. Despite a well-described role of Syndecan-4 during cell movement, information is scarce regarding specific Syndecan-4 partners involved in Thy-1/CD90-stimulated cell migration.
methodsMass spectrometry (MS) analysis of complexes precipitated with the Syndecan-4 cytoplasmic tail peptide was used to identify potential Syndecan-4-binding partners. The interactions found by MS were validated by immunoprecipitation and proximity ligation assays. The conducted research employed an array of genetic, biochemical and pharmacological approaches, including: PAR-3, Syndecan-4 and Tiam1 silencing, active Rac1 GEFs affinity precipitation, and video microscopy.
resultsWe identified PAR-3 as a Syndecan-4-binding protein. Its interaction depended on the carboxy-terminal EFYA sequence present on Syndecan-4. In astrocytes where PAR-3 expression was reduced, Thy-1-induced cell migration and focal adhesion disassembly was impaired. This effect was associated with a sustained Focal Adhesion Kinase activation in the siRNA-PAR-3 treated cells. Our data also show that Thy-1/CD90 activates Tiam1, a PAR-3 effector. Additionally, we found that after Syndecan-4 silencing, Tiam1 activation was decreased and it was no longer recruited to the membrane. Syndecan-4/PAR-3 interaction and the alteration in focal adhesion dynamics were validated in mouse embryonic fibroblast (MEF) cells, thereby identifying this novel Syndecan-4/PAR-3 signaling complex as a general mechanism for mesenchymal cell migration involved in Thy-1/CD90 stimulation.
conclusionsThe newly identified Syndecan-4/PAR-3 signaling complex participates in Thy-1/CD90-induced focal adhesion disassembly in mesenchymal cells. The mechanism involves focal adhesion kinase dephosphorylation and Tiam1 activation downstream of Syndecan-4/PAR-3 signaling complex formation. Additionally, PAR-3 is defined here as a novel adhesome-associated component with an essential role in focal adhesion disassembly during polarized cell migration. These novel findings uncover signaling mechanisms regulating cell migration, thereby opening up new avenues for future research on Syndecan-4/PAR-3 signaling in processes such as wound healing and scarring.
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