Syndecan-4/PAR-3 signaling regulates focal adhesion dynamics in mesenchymal cells
Abstract Background 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...
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Format: | Article |
Language: | English |
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BMC
2020-08-01
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Series: | Cell Communication and Signaling |
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Online Access: | http://link.springer.com/article/10.1186/s12964-020-00629-3 |
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doaj-d6664e34183148169b7735a292650ae3 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alejandra Valdivia Areli Cárdenas Marianne Brenet Horacio Maldonado Milene Kong Jorge Díaz Keith Burridge Pascal Schneider Alejandra San Martín Rafael García-Mata Andrew F. G. Quest Lisette Leyton |
spellingShingle |
Alejandra Valdivia Areli Cárdenas Marianne Brenet Horacio Maldonado Milene Kong Jorge Díaz Keith Burridge Pascal Schneider Alejandra San Martín Rafael García-Mata Andrew F. G. Quest Lisette Leyton Syndecan-4/PAR-3 signaling regulates focal adhesion dynamics in mesenchymal cells Cell Communication and Signaling Focal adhesion turnover Cytoskeleton Cell polarity Mesenchymal cell migration Wound healing |
author_facet |
Alejandra Valdivia Areli Cárdenas Marianne Brenet Horacio Maldonado Milene Kong Jorge Díaz Keith Burridge Pascal Schneider Alejandra San Martín Rafael García-Mata Andrew F. G. Quest Lisette Leyton |
author_sort |
Alejandra Valdivia |
title |
Syndecan-4/PAR-3 signaling regulates focal adhesion dynamics in mesenchymal cells |
title_short |
Syndecan-4/PAR-3 signaling regulates focal adhesion dynamics in mesenchymal cells |
title_full |
Syndecan-4/PAR-3 signaling regulates focal adhesion dynamics in mesenchymal cells |
title_fullStr |
Syndecan-4/PAR-3 signaling regulates focal adhesion dynamics in mesenchymal cells |
title_full_unstemmed |
Syndecan-4/PAR-3 signaling regulates focal adhesion dynamics in mesenchymal cells |
title_sort |
syndecan-4/par-3 signaling regulates focal adhesion dynamics in mesenchymal cells |
publisher |
BMC |
series |
Cell Communication and Signaling |
issn |
1478-811X |
publishDate |
2020-08-01 |
description |
Abstract Background 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. Graphical abstract |
topic |
Focal adhesion turnover Cytoskeleton Cell polarity Mesenchymal cell migration Wound healing |
url |
http://link.springer.com/article/10.1186/s12964-020-00629-3 |
work_keys_str_mv |
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doaj-d6664e34183148169b7735a292650ae32020-11-25T03:49:38ZengBMCCell Communication and Signaling1478-811X2020-08-0118111910.1186/s12964-020-00629-3Syndecan-4/PAR-3 signaling regulates focal adhesion dynamics in mesenchymal cellsAlejandra Valdivia0Areli Cárdenas1Marianne Brenet2Horacio Maldonado3Milene Kong4Jorge Díaz5Keith Burridge6Pascal Schneider7Alejandra San Martín8Rafael García-Mata9Andrew F. G. Quest10Lisette Leyton11Cellular Communication Laboratory, Program of Cellular & Molecular Biology, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de ChileCellular Communication Laboratory, Program of Cellular & Molecular Biology, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de ChileCellular Communication Laboratory, Program of Cellular & Molecular Biology, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de ChileCellular Communication Laboratory, Program of Cellular & Molecular Biology, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de ChileCellular Communication Laboratory, Program of Cellular & Molecular Biology, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de ChileCellular Communication Laboratory, Program of Cellular & Molecular Biology, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de ChileDepartment of Cell Biology and Physiology, University of North Carolina at Chapel HillDepartment of Biochemistry, University of LausanneSchool of Medicine, Division of Cardiology, Emory UniversityDepartment of Biological Sciences, University of ToledoCellular Communication Laboratory, Program of Cellular & Molecular Biology, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de ChileCellular Communication Laboratory, Program of Cellular & Molecular Biology, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de ChileAbstract Background 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. Graphical abstracthttp://link.springer.com/article/10.1186/s12964-020-00629-3Focal adhesion turnoverCytoskeletonCell polarityMesenchymal cell migrationWound healing |