Syndecan-4/PAR-3 signaling regulates focal adhesion dynamics in mesenchymal cells

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dc.contributor.authorAlejandra Valdivia
dc.contributor.authorAreli Cárdena
dc.contributor.authorMarianne Brenet
dc.contributor.authorHoracio Maldonado
dc.contributor.authorMilen Kong
dc.contributor.authorJorge Díaz
dc.contributor.authorKeith Burridge
dc.contributor.authorPascal Schneider
dc.contributor.authorAlejandra San Martín
dc.contributor.authorRafael García-Mata
dc.contributor.authorAndrew F.G. Quest
dc.contributor.authorLisette Leyton
dc.date.accessioned2025-05-29T14:41:25Z
dc.date.available2025-05-29T14:41:25Z
dc.date.issued2020
dc.description.abstractBackground: Syndecans 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. Methods: Mass 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. Results: We 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. Conclusions: The 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
dc.description.sponsorshipFONDECYT #1150744, #1200836, #1170925, #3140471, # 3160349, #3170169. CONICYT-FONDAP #15130011 National Institutes of Health HL113167 National Institutes of Health GM029860 National Institutes of Health 1R21CA194776-01A1, 1R15CA199101-01A1 Swiss National Science Foundation 31003A_176256
dc.identifier.doi10.1186/s12964-020-00629-3
dc.identifier.issn1478811X
dc.identifier.urihttps://repositorioabierto.uantof.cl/handle/uantof/494
dc.language.isoen
dc.rights.licensehttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceCell Communication and Signaling
dc.titleSyndecan-4/PAR-3 signaling regulates focal adhesion dynamics in mesenchymal cells
dc.typeArticle
oaire.citation.volume18
organization.identifier.rorUniversidad de Antofagasta
uantof.identificator.departmentDepartamento Biomédico
uantof.identificator.facultyFacultad de Ciencias de la Salud
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