2024
Endothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis
Joshi D, Coon B, Chakraborty R, Deng H, Yang Z, Babar M, Fernandez-Tussy P, Meredith E, Attanasio J, Joshi N, Traylor J, Orr A, Fernandez-Hernando C, Libreros S, Schwartz M. Endothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis. Nature Cardiovascular Research 2024, 3: 1035-1048. PMID: 39232138, PMCID: PMC11399086, DOI: 10.1038/s44161-024-00522-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisCadherin Related ProteinsCadherinsDisease Models, AnimalEndothelial CellsHuman Umbilical Vein Endothelial CellsHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMiceMice, Inbred C57BLMice, KnockoutPlaque, AtheroscleroticReceptors, NotchSignal TransductionConceptsAtherosclerotic cardiovascular diseaseIntracellular domainNotch intracellular domainTranscription factor KLF2Mechanisms of vascular inflammationAnti-inflammatory programVascular endothelial cellsHost defenseCleavage resultsAntibody blockadeGenetic deletionVascular inflammationViral infectionImmune systemEndothelial cellsCardiovascular diseasePromote atherosclerosisBlood flowKLF2KLF4Suppressive signalsEndotheliumMechanistic studiesAfadin–nectin forces its way to the front
Sebbagh M, Schwartz M. Afadin–nectin forces its way to the front. Journal Of Cell Biology 2024, 223: e202403177. PMID: 38563860, PMCID: PMC10988649, DOI: 10.1083/jcb.202403177.Peer-Reviewed Original Research
2017
Live imaging molecular changes in junctional tension upon VE-cadherin in zebrafish
Lagendijk AK, Gomez GA, Baek S, Hesselson D, Hughes WE, Paterson S, Conway DE, Belting HG, Affolter M, Smith KA, Schwartz MA, Yap AS, Hogan BM. Live imaging molecular changes in junctional tension upon VE-cadherin in zebrafish. Nature Communications 2017, 8: 1402. PMID: 29123087, PMCID: PMC5680264, DOI: 10.1038/s41467-017-01325-6.Peer-Reviewed Original ResearchConceptsVE-cadherinEndothelial cell-cell junctionsCell-cell junctionsActo-myosin cytoskeletonTension sensorActo-myosin contractilityJunctional tensionEmbryonic developmentDiverse rolesVascular developmentLive zebrafishChemical perturbationsFRET measurementsZebrafishAdjacent cellsMolecular changesEndothelial cellsCellsBiosensor approachCytoskeletonHomeostasisLocalizationVivoTensile changesMaturesVE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN
Conway DE, Coon BG, Budatha M, Arsenovic PT, Orsenigo F, Wessel F, Zhang J, Zhuang Z, Dejana E, Vestweber D, Schwartz MA. VE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN. Current Biology 2017, 27: 2219-2225.e5. PMID: 28712573, PMCID: PMC5667920, DOI: 10.1016/j.cub.2017.06.020.Peer-Reviewed Original ResearchConceptsSrc family kinasesProtein LGNCytoplasmic tyrosinesVE-cadherinVascular endothelial growth factor receptorVE-cadherin functionJunctional complexesRespective cytoplasmic domainsBlood vessel developmentVE-cadherin phosphorylationTransduce forcesTransduce signalsCytoplasmic domainFamily kinasesBlood vessel remodelingGrowth factor receptorVEGFR activationPECAM-1Stress responseComplex consistingFluid shear stressVessel developmentFlow-dependent vascular remodelingSpecific poolPhosphorylation
2015
Intramembrane binding of VE-cadherin to VEGFR2 and VEGFR3 assembles the endothelial mechanosensory complex
Coon BG, Baeyens N, Han J, Budatha M, Ross TD, Fang JS, Yun S, Thomas JL, Schwartz MA. Intramembrane binding of VE-cadherin to VEGFR2 and VEGFR3 assembles the endothelial mechanosensory complex. Journal Of Cell Biology 2015, 208: 975-986. PMID: 25800053, PMCID: PMC4384728, DOI: 10.1083/jcb.201408103.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDCadherinsCell MovementCells, CulturedEndothelium, VascularHEK293 CellsHuman Umbilical Vein Endothelial CellsHumansMechanotransduction, CellularMiceMice, Inbred C57BLNeovascularization, PhysiologicPlaque, AtheroscleroticPlatelet Endothelial Cell Adhesion Molecule-1Protein Structure, TertiaryRNA InterferenceRNA, Small InterferingStress, MechanicalStress, PhysiologicalVascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-3ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation
Tornavaca O, Chia M, Dufton N, Almagro LO, Conway DE, Randi AM, Schwartz MA, Matter K, Balda MS. ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation. Journal Of Cell Biology 2015, 208: 821-838. PMID: 25753039, PMCID: PMC4362456, DOI: 10.1083/jcb.201404140.Peer-Reviewed Original ResearchMeSH KeywordsActomyosinAdherens JunctionsAnimalsAntigens, CDCadherinsCapillary PermeabilityCell Adhesion MoleculesCell MovementCells, CulturedClaudin-5Cytoskeletal ProteinsCytoskeletonEndothelial CellsHumansMechanotransduction, CellularMice, Inbred C57BLMyosinsNeovascularization, PhysiologicProtein TransportReceptors, Cell SurfaceTight JunctionsZonula Occludens-1 ProteinConceptsCell-cell tensionAdherens junctionsActive myosin IIZO-1VE-cadherinBarrier formationEndothelial adherens junctionsJunctional recruitmentPrimary endothelial cellsCadherin complexActomyosin organizationCentral regulatorStress fibersInhibition of ROCKMyosin IIProtein ZO-1Tight junction protein ZO-1Cell migrationIntercellular junctionsP114RhoGEFMechanotransducersTight junctionsEndothelial junctionsEndothelial cellsTight junction disruptionRac1 functions as a reversible tension modulator to stabilize VE-cadherin trans-interaction
Daneshjou N, Sieracki N, van Nieuw Amerongen GP, Conway D, Schwartz M, Komarova Y, Malik A. Rac1 functions as a reversible tension modulator to stabilize VE-cadherin trans-interaction. Journal Of Cell Biology 2015, 208: 23-32. PMID: 25559184, PMCID: PMC4284224, DOI: 10.1083/jcb.201409108.Peer-Reviewed Original ResearchActomyosinAdherens JunctionsAntigens, CDCadherinsCell AdhesionCells, CulturedEndothelial CellsEnzyme ActivationHumansKineticsMicroscopy, FluorescenceMicroscopy, VideoModels, BiologicalMyosin Type IIProtein BindingProtein Kinase InhibitorsProtein MultimerizationProtein StabilityRac1 GTP-Binding ProteinRho-Associated KinasesTime-Lapse ImagingTransfection
2014
Mechanotransduction of shear stress occurs through changes in VE-cadherin and PECAM-1 tension: Implications for cell migration
Conway DE, Schwartz MA. Mechanotransduction of shear stress occurs through changes in VE-cadherin and PECAM-1 tension: Implications for cell migration. Cell Adhesion & Migration 2014, 9: 335-339. PMID: 25482618, PMCID: PMC4955370, DOI: 10.4161/19336918.2014.968498.Peer-Reviewed Original ResearchTension-Sensitive Actin Assembly Supports Contractility at the Epithelial Zonula Adherens
Leerberg JM, Gomez GA, Verma S, Moussa EJ, Wu SK, Priya R, Hoffman BD, Grashoff C, Schwartz MA, Yap AS. Tension-Sensitive Actin Assembly Supports Contractility at the Epithelial Zonula Adherens. Current Biology 2014, 24: 1689-1699. PMID: 25065757, PMCID: PMC5103636, DOI: 10.1016/j.cub.2014.06.028.Peer-Reviewed Original ResearchConceptsMena/VASPActin assemblyEpithelial zonula adherensZonula adherensMyosin II activationActin filament turnoverCadherin junctionsActomyosin apparatusVASP proteinsActin scaffoldFilament turnoverActin filamentsJunctional integrityVinculinPhysical interactionTissue integrityActomyosin systemEpithelial cellsAdherensAssemblyContractile apparatusRegulationVASPEffective contractilityUnderlying mechanism
2013
Fluid Shear Stress on Endothelial Cells Modulates Mechanical Tension across VE-Cadherin and PECAM-1
Conway DE, Breckenridge MT, Hinde E, Gratton E, Chen CS, Schwartz MA. Fluid Shear Stress on Endothelial Cells Modulates Mechanical Tension across VE-Cadherin and PECAM-1. Current Biology 2013, 23: 1024-1030. PMID: 23684974, PMCID: PMC3676707, DOI: 10.1016/j.cub.2013.04.049.Peer-Reviewed Original ResearchConceptsFluid shear stressVE-cadherinCell-cell junctionsPECAM-1Junctional tensionCytoskeletal remodelingVascular morphogenesisGene expressionComplex consistingCells triggersFlow-dependent vascular remodelingIon channelsFRET measurementsEndothelial cells triggersMechanical tensionNormal vascular functionTension sensorDetectable tensionEC responseStatic cultureJunctional receptorsRemodelingCytoskeletonMorphogenesisVascular remodelingN-cadherin regulates spatially polarized signals through distinct p120ctn and β-catenin-dependent signalling pathways
Ouyang M, Lu S, Kim T, Chen CE, Seong J, Leckband DE, Wang F, Reynolds AB, Schwartz MA, Wang Y. N-cadherin regulates spatially polarized signals through distinct p120ctn and β-catenin-dependent signalling pathways. Nature Communications 2013, 4: 1589. PMID: 23481397, PMCID: PMC3602931, DOI: 10.1038/ncomms2560.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAnimalsBeta CateninCadherinsCateninsCell PolarityChickensCHO CellsCricetinaeDelta CateninEmbryo, MammalianFibroblastsFluorescent DyesIntegrinsIntercellular JunctionsMiceModels, BiologicalPhosphatidylinositol 3-KinasesProtein BindingRac GTP-Binding ProteinsRatsRecombinant Fusion ProteinsRNA, Small InterferingSignal TransductionConceptsMyosin II light chainRac activityActin filamentsSmall GTPase RacΒ-catenin-dependent signaling pathwaysHigher phosphoinositidesCellular functionsGTPase RacDistinct effectorsMolecular signalsSignaling pathwaysMolecular activityLight chainNeighbouring cellsN-cadherinPhosphoinositideIntercellular junctionsIntegrin α5RacCellsComplexesFilamentsP120ctnSpatial distributionEffectors
2009
Cadherin Adhesion, Tissue Tension, and Noncanonical Wnt Signaling Regulate Fibronectin Matrix Organization
Dzamba BJ, Jakab KR, Marsden M, Schwartz MA, DeSimone DW. Cadherin Adhesion, Tissue Tension, and Noncanonical Wnt Signaling Regulate Fibronectin Matrix Organization. Developmental Cell 2009, 16: 421-432. PMID: 19289087, PMCID: PMC2682918, DOI: 10.1016/j.devcel.2009.01.008.Peer-Reviewed Original ResearchConceptsCadherin adhesionBlastocoel roofPlanar cell polarity signalingMatrix assemblyCell polarity signalingCell-cell adhesionFN fibril formationFN fibril assemblyPolarity signalingFocal adhesionsActin reorganizationXenopus embryosRegulatory pathwaysMyosin contractilityFibronectin matrixMatrix organizationSpatiotemporal localizationCultured cellsCell surfaceAnalogous roleFibril formationFibril assemblyFibrillar matrixMechanical tensionAssembly
2008
Regulation of LKB1/STRAD Localization and Function by E-Cadherin
Sebbagh M, Santoni MJ, Hall B, Borg JP, Schwartz MA. Regulation of LKB1/STRAD Localization and Function by E-Cadherin. Current Biology 2008, 19: 37-42. PMID: 19110428, PMCID: PMC2773019, DOI: 10.1016/j.cub.2008.11.033.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Vesicular TransportAdherens JunctionsAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesBlotting, WesternCaco-2 CellsCadherinsCell FractionationDNA PrimersFluorescence Resonance Energy TransferHumansMultiprotein ComplexesPhosphorylationProtein Serine-Threonine KinasesReverse Transcriptase Polymerase Chain ReactionConceptsAdherens junctionsLKB1 complexE-cadherinE-cadherin-mediated adherens junctionsAMPK phosphorylationEpithelial apicobasal polarityCell-matrix contactsCell energy metabolismPseudokinase STRADLKB1 kinaseProtein MO25Apicobasal polarityEpithelial polarityCellular processesFluorescence resonance energy transferFamily kinasesKinase activityTumor suppressionTumor suppressorResonance energy transferKinaseUpstream factorsEnergy metabolismSTRADEpithelial cellsCell adhesion receptors in mechanotransduction
Schwartz MA, DeSimone DW. Cell adhesion receptors in mechanotransduction. Current Opinion In Cell Biology 2008, 20: 551-556. PMID: 18583124, PMCID: PMC2581799, DOI: 10.1016/j.ceb.2008.05.005.Peer-Reviewed Original ResearchConceptsAdhesion receptorsCell fate decisionsCadherin-mediated adhesionCell adhesion receptorsFate decisionsMorphogenetic movementsTissue-level responsesCultured cellsExtracellular matrixMechanotransductionLevel responseCellsCytoskeletonCadherinReceptorsOrganismsAdhesionIntegrinsPathwayMechanical stimulationIntracellularMechanismMechanical stressResponseCentral mechanisms
2005
Integrin-dependent actomyosin contraction regulates epithelial cell scattering
de Rooij J, Kerstens A, Danuser G, Schwartz MA, Waterman-Storer CM. Integrin-dependent actomyosin contraction regulates epithelial cell scattering. Journal Of Cell Biology 2005, 171: 153-164. PMID: 16216928, PMCID: PMC2171213, DOI: 10.1083/jcb.200506152.Peer-Reviewed Original ResearchConceptsCell-cell junctionsEpithelial cell scatteringCell-cell adhesionCell scatteringHepatocyte growth factorE-cadherin functionMadin-Darby canine kidneyMyosin regulatory light chainExtracellular matrix proteinsTime-lapse imagingPossible cross talkCarcinoma cell invasionTraction forceRegulatory light chainIntegrin adhesionEpithelial-mesenchymal transitionActomyosin contractionMatrix proteinsCell invasionHigh traction forceMimic key aspectsCross talkSubstrate complianceGrowth factorCanine kidneyA mechanosensory complex that mediates the endothelial cell response to fluid shear stress
Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, Engelhardt B, Cao G, DeLisser H, Schwartz MA. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 2005, 437: 426-431. PMID: 16163360, DOI: 10.1038/nature03952.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDCadherinsCattleCell AdhesionCells, CulturedEndothelial CellsFemaleGene DeletionMechanotransduction, CellularMiceMice, KnockoutMultiprotein ComplexesNF-kappa BPlatelet Endothelial Cell Adhesion Molecule-1RatsStress, MechanicalVascular Endothelial Growth Factor Receptor-2ConceptsDownstream inflammatory genesPECAM-1 knockout miceVascular endothelial cell cadherinVascular remodellingHigh-affinity stateInflammatory genesNF-κBVascular homeostasisEndothelial cell responsesCell responsesMechanosensory complexPECAM-1Heterologous cellsPathway upstreamCardiac developmentIntegrin activationAtherogenesisMechanism of transductionPathwayMice
2004
VE-cadherin Links tRNA Synthetase Cytokine to Anti-angiogenic Function*
Tzima E, Reader JS, Irani-Tehrani M, Ewalt KL, Schwartz MA, Schimmel P. VE-cadherin Links tRNA Synthetase Cytokine to Anti-angiogenic Function*. Journal Of Biological Chemistry 2004, 280: 2405-2408. PMID: 15579907, DOI: 10.1074/jbc.c400431200.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acyl-tRNA SynthetasesAngiogenesis InhibitorsAnimalsAntigens, CDAortaBlotting, WesternCadherinsCattleCell MovementCells, CulturedCytokinesEndothelium, VascularEnzyme ActivationExtracellular Signal-Regulated MAP KinasesGap JunctionsGreen Fluorescent ProteinsImmunoprecipitationMicroscopy, ConfocalMicroscopy, FluorescenceNeovascularization, PathologicProtein BindingRecombinant ProteinsSignal TransductionTryptophan-tRNA LigaseVascular Endothelial Growth Factor AConceptsT2-TrpRS