title: VASP, zyxin and TES are tension-dependent members of Focal Adherens Junctions independent of the α-catenin-vinculin module.
abstract: 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.
authors.affiliation: Dept. Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Stratenum 3.231, Universiteitsweg 100, 3584 CG, Utrecht, the Netherlands.
authors.forename: Joppe
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: Dept. Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Stratenum 3.231, Universiteitsweg 100, 3584 CG, Utrecht, the Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: van der Krogt
authors.affiliation: Dept. Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Stratenum 3.231, Universiteitsweg 100, 3584 CG, Utrecht, the Netherlands.
authors.forename: Floor
authors.initials: F
authors.lastname: Twiss
authors.affiliation: Dept. Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Stratenum 3.231, Universiteitsweg 100, 3584 CG, Utrecht, the Netherlands.
authors.forename: Annika
authors.initials: A
authors.lastname: Bongaarts
authors.affiliation: Dept. Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Stratenum 3.231, Universiteitsweg 100, 3584 CG, Utrecht, the Netherlands.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Habani
authors.affiliation: Erasmus Optical Imaging Center, Department of Pathology, Erasmus MC, Dr. Molewaterplein 50-60, 3015 GE Rotterdam, the Netherlands.
authors.forename: Johan A
authors.initials: JA
authors.lastname: Slotman
authors.affiliation: Erasmus Optical Imaging Center, Department of Pathology, Erasmus MC, Dr. Molewaterplein 50-60, 3015 GE Rotterdam, the Netherlands.
authors.forename: Adriaan
authors.initials: A
authors.lastname: Houtsmuller
authors.affiliation: Department of Molecular Cell Biology, Sanquin Research and Swammerdam Institute for Life Sciences, University of Amsterdam. Plesmanlaan 125, 1066 CX, Amsterdam, the Netherlands.
authors.forename: Stephan
authors.initials: S
authors.lastname: Huveneers
authors.affiliation: Dept. Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Stratenum 3.231, Universiteitsweg 100, 3584 CG, Utrecht, the Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: de Rooij
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D000199:Actins / Q000235:genetics* / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001696:Biomechanical Phenomena; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004285:Dogs; D022001:Focal Adhesions / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics* / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D040542:Mechanotransduction, Cellular; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D016601:RNA-Binding Proteins; D016596:Vinculin / Q000235:genetics / Q000378:metabolism; D060589:Zyxin / Q000235:genetics* / Q000378:metabolism; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; C429688:TES protein, human; C488955:VCL protein, human; C092842:ZYX protein, human; D060589:Zyxin; D051178:alpha Catenin; D000098662:Vasodilator-Stimulated Phosphoprotein; D016596:Vinculin