{"doi":"10.1038/srep17225","title":"VASP, zyxin and TES are tension-dependent members of Focal Adherens Junctions independent of the α-catenin-vinculin module","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Mechanical forces are integrated at cadherin-based adhesion complexes to regulate morphology and strength of cell-cell junctions and organization of associated F-actin. A central mechanosensor at the cadherin complex is α-catenin, whose stretching recruits vinculin to regulate adhesion strength. The identity of the F-actin regulating signals that are also activated by mechanical forces at cadherin-based junctions has remained elusive. Here we identify the actin-regulators VASP, zyxin and TES as members of punctate, tensile cadherin-based junctions called Focal Adherens Junctions (FAJ) and show that they display mechanosensitive recruitment similar to that of vinculin. However, this recruitment is not altered by destroying or over-activating the α-catenin/vinculin module. Structured Illumination Microscopy (SIM) indicates that these tension sensitive proteins concentrate at locations within FAJs that are distinct from the core cadherin complex proteins. Furthermore, localization studies using mutated versions of VASP and zyxin indicate that these two proteins require binding to each other in order to localize to the FAJs. We conclude that there are multiple force sensitive modules present at the FAJ that are activated at distinct locations along the cadherin-F-actin axis and regulate specific aspects of junction dynamics.</jats:p>","journal":"Scientific Reports","year":2015,"id":684513,"datarank":0.6554171778700533,"base_score":4.3694478524670215,"endowment":4.3694478524670215,"self_citation_contribution":0.6554171778700533,"citation_network_contribution":0.0,"self_endowment_contribution":0.6554171778700533,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":78,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1788288,"name":"Gerard van der Krogt","orcid":null,"position":1,"is_corresponding":false},{"id":1788289,"name":"Floor Twiss","orcid":null,"position":2,"is_corresponding":false},{"id":1788290,"name":"Annika Bongaarts","orcid":null,"position":3,"is_corresponding":false},{"id":1788291,"name":"Yasmin Habani","orcid":null,"position":4,"is_corresponding":false},{"id":1788292,"name":"Johan A. Slotman","orcid":null,"position":5,"is_corresponding":false},{"id":1788293,"name":"Adriaan Houtsmuller","orcid":null,"position":6,"is_corresponding":false},{"id":294517,"name":"Stephan Huveneers","orcid":"0000-0002-1091-475X","position":7,"is_corresponding":false},{"id":589825,"name":"Johan de Rooij","orcid":"0000-0001-6101-7875","position":8,"is_corresponding":false},{"id":1788287,"name":"Joppe Oldenburg","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"VASP, zyxin and TES are tension-dependent members of Focal Adherens Junctions independent of the α-catenin-vinculin module","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Mechanical forces are integrated at cadherin-based adhesion complexes to regulate morphology and strength of cell-cell junctions and organization of associated F-actin. A central mechanosensor at the cadherin complex is α-catenin, whose stretching recruits vinculin to regulate adhesion strength. The identity of the F-actin regulating signals that are also activated by mechanical forces at cadherin-based junctions has remained elusive. Here we identify the actin-regulators VASP, zyxin and TES as members of punctate, tensile cadherin-based junctions called Focal Adherens Junctions (FAJ) and show that they display mechanosensitive recruitment similar to that of vinculin. However, this recruitment is not altered by destroying or over-activating the α-catenin/vinculin module. Structured Illumination Microscopy (SIM) indicates that these tension sensitive proteins concentrate at locations within FAJs that are distinct from the core cadherin complex proteins. Furthermore, localization studies using mutated versions of VASP and zyxin indicate that these two proteins require binding to each other in order to localize to the FAJs. We conclude that there are multiple force sensitive modules present at the FAJ that are activated at distinct locations along the cadherin-F-actin axis and regulate specific aspects of junction dynamics.</jats:p>","is_dataset_classified":null,"base_score":4.3694478524670215,"endowment":4.3694478524670215,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26611125","pmcid":"PMC4661603","openalex_id":"https://openalex.org/W2443492442","authors":[],"funders":[{"funder_name":"Dutch Research Council (NWO)","grant_id":"016.156.327","title":null},{"funder_name":"Worldwide Cancer Research","grant_id":"13-0300","title":null},{"funder_name":"Netherlands Organisation for Scientific Research (NWO)","grant_id":"050-060-621","title":"Systems Biology Consortium NCSB AddOn"},{"funder_name":"Netherlands Organisation for Scientific Research (NWO)","grant_id":"17225","title":"Senior expert on ‘ecological intensification of aquaculture’"}],"total_grants":4,"fwci":3.1952,"citation_percentile":0.92129368,"influential_citations":0,"citation_trend":[{"year":2016,"count":7},{"year":2017,"count":7},{"year":2018,"count":8},{"year":2019,"count":6},{"year":2020,"count":5},{"year":2021,"count":14},{"year":2022,"count":7},{"year":2023,"count":6},{"year":2024,"count":9},{"year":2025,"count":4},{"year":2026,"count":5}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/srep17225.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/srep17225.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/srep17225","host_type":"publisher"},{"url":"https://doi.org/10.1038/srep17225","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26611125","host_type":"repository"},{"url":"https://pure.eur.nl/en/publications/2b8325e9-a0ce-48cb-85fe-edf0ffd9f60b","host_type":"repository"},{"url":"http://doi.org/10.1038/srep17225","host_type":"repository"},{"url":"http://hdl.handle.net/1765/82558","host_type":"repository"},{"url":"https://repub.eur.nl/pub/82558","host_type":"repository"},{"url":"https://dspace.library.uu.nl/handle/1874/333462","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4661603","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4661603?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1038/srep17225","host_type":""},{"url":"https://dx.doi.org/10.1038/srep17225","host_type":""}],"fields_of_study":["Cellular Mechanics and Interactions","Heat shock proteins research","Skin and Cellular Biology Research","0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":["Vasodilator-Stimulated Phosphoprotein","Actins","Animals","Biomechanical Phenomena","Cell Adhesion","Cytoskeletal Proteins","Dogs","Gene Expression Regulation","Humans","Microfilament Proteins","Actin Cytoskeleton","Mutation","Phosphoproteins","Protein Binding","Cell Adhesion Molecules","Vinculin","RNA-Binding Proteins","Focal Adhesions","Adherens Junctions","Mechanotransduction, Cellular","alpha Catenin","HEK293 Cells","LIM Domain Proteins","Zyxin","Human Umbilical Vein Endothelial Cells","Madin Darby Canine Kidney Cells"],"keywords":["Adherens junction","Vinculin","Cadherin","Focal adhesion","Cell biology","Catenin","Actin","Actin cytoskeleton","Adhesion","Cell adhesion","Chemistry","Cytoskeleton","Biology","Cell","Wnt signaling pathway","Signal transduction","Biochemistry","Mechanotransduction, Cellular","Article","Madin Darby Canine Kidney Cells","Dogs","Human Umbilical Vein Endothelial Cells","Animals","Humans","Focal Adhesions","Microfilament Proteins","Adherens Junctions","EMC MM-03-24-01","LIM Domain Proteins","Phosphoproteins","Actins","Biomechanical Phenomena","Cytoskeletal Proteins","HEK293 Cells","Gene Expression Regulation","Mutation","Cell Adhesion Molecules"],"sdg_mappings":[{"sdg_number":10,"sdg_label":"10. 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