2019
Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis
Chen PY, Qin L, Li G, Wang Z, Dahlman JE, Malagon-Lopez J, Gujja S, Cilfone N, Kauffman K, Sun L, Sun H, Zhang X, Aryal B, Canfran-Duque A, Liu R, Kusters P, Sehgal A, Jiao Y, Anderson D, Gulcher J, Fernandez-Hernando C, Lutgens E, Schwartz M, Pober J, Chittenden T, Tellides G, Simons M. Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis. Nature Metabolism 2019, 1: 912-926. PMID: 31572976, PMCID: PMC6767930, DOI: 10.1038/s42255-019-0102-3.Peer-Reviewed Original ResearchConceptsTGF-β signalingVascular inflammationDisease progressionPlaque growthProgressive vascular diseaseVessel wall inflammationChronic inflammatory responseSpecific therapeutic interventionsAtherosclerotic plaque growthHyperlipidemic micePlaque inflammationWall inflammationProinflammatory effectsVascular diseaseInflammatory responseVascular permeabilityAtherosclerotic plaquesAbnormal shear stressTherapeutic interventionsInflammationEndothelial TGFΒ signalingVessel wallAtherosclerosisLipid retentionMicroRNA-dependent regulation of biomechanical genes establishes tissue stiffness homeostasis
Moro A, Driscoll TP, Boraas LC, Armero W, Kasper DM, Baeyens N, Jouy C, Mallikarjun V, Swift J, Ahn SJ, Lee D, Zhang J, Gu M, Gerstein M, Schwartz M, Nicoli S. MicroRNA-dependent regulation of biomechanical genes establishes tissue stiffness homeostasis. Nature Cell Biology 2019, 21: 348-358. PMID: 30742093, PMCID: PMC6528464, DOI: 10.1038/s41556-019-0272-y.Peer-Reviewed Original ResearchConceptsArgonaute 2MicroRNA-dependent regulationMechanical homeostasisMicroRNA recognition elementsExtracellular matrix proteinsZebrafish finsMicroRNA familiesTarget mRNAsVertebrate tissuesHyper-contractile phenotypesRegulatory pathwaysUntranslated regionRecognition elementMatrix proteinsComprehensive identificationCaM mRNAConnective tissue growth factorExtracellular matrix depositionHomeostasisTissue growth factorMRNAFibroblast cellsMicroRNAsGrowth factorSoft substrates
2016
Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development
Wang Y, Baeyens N, Corti F, Tanaka K, Fang JS, Zhang J, Jin Y, Coon B, Hirschi KK, Schwartz MA, Simons M. Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development. Development 2016, 143: 4441-4451. PMID: 27789626, PMCID: PMC5201046, DOI: 10.1242/dev.140129.Peer-Reviewed Original ResearchConceptsLymphatic endothelial cellsPlanar cell polarity protein Vangl2Lymphatic vessel remodelingMouse embryonic developmentHuman lymphatic endothelial cellsVangl2 overexpressionVangl2 expressionEmbryonic developmentValve morphogenesisEndothelial cellsVasculature developmentSyndecan-4Lymphatic vasculatureFluid shear stressSDC4Double knockout miceMice resultsHigh expressionVessel remodelingLymphatic vesselsExpressionVangl2RemodelingCellsMorphogenesisForce regulated conformational change of integrin αVβ3
Chen Y, Lee H, Tong H, Schwartz M, Zhu C. Force regulated conformational change of integrin αVβ3. Matrix Biology 2016, 60: 70-85. PMID: 27423389, PMCID: PMC5237428, DOI: 10.1016/j.matbio.2016.07.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomechanical PhenomenaBiotinylationCell AdhesionCell LineEndothelial CellsErythrocytesExtracellular MatrixFibronectinsGene ExpressionGlassHumansIntegrin alphaVbeta3KineticsLungMiceMolecular ProbesPoint MutationProtein BindingProtein ConformationSignal TransductionSingle Molecule ImagingConceptsConformational changesTransduce signalsSingle-molecule levelIntegrin functionBiomembrane force probeMolecular machinesPhysiological functionsCell adhesionCell surfaceExtracellular matrixPoint mutationsConformational transitionIntegrinsEssential roleTumor metastasisExtended conformationConformationDynamic equilibriumEctodomainMutationsForce probePhagocytosisMembraneAngiogenesisFunctionComparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine
Balestrini JL, Gard AL, Gerhold KA, Wilcox EC, Liu A, Schwan J, Le AV, Baevova P, Dimitrievska S, Zhao L, Sundaram S, Sun H, Rittié L, Dyal R, Broekelmann TJ, Mecham RP, Schwartz MA, Niklason LE, White ES. Comparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine. Biomaterials 2016, 102: 220-230. PMID: 27344365, PMCID: PMC4939101, DOI: 10.1016/j.biomaterials.2016.06.025.Peer-Reviewed Original ResearchConceptsHuman endothelial cellsCell-matrix interactionsLung regenerationEndothelial cellsKey matrix proteinsComparative biologyCell adhesion moleculeMatrix proteinsLung extracellular matrixCell healthExtracellular matrixResidual DNASpecies mismatchRat lung scaffoldsRegenerative medicineAdhesion moleculesLung scaffoldsPrimate tissuesCellsVascular cell adhesion moleculeLung engineeringLung matrixLess expressionPulmonary cellsProfound effect
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 remodeling
2012
Neuropilin-1 Stimulates Tumor Growth by Increasing Fibronectin Fibril Assembly in the Tumor Microenvironment
Yaqoob U, Cao S, Shergill U, Jagavelu K, Geng Z, Yin M, de Assuncao TM, Cao Y, Szabolcs A, Thorgeirsson S, Schwartz M, Yang JD, Ehman R, Roberts L, Mukhopadhyay D, Shah VH. Neuropilin-1 Stimulates Tumor Growth by Increasing Fibronectin Fibril Assembly in the Tumor Microenvironment. Cancer Research 2012, 72: 4047-4059. PMID: 22738912, PMCID: PMC3421041, DOI: 10.1158/0008-5472.can-11-3907.Peer-Reviewed Original ResearchConceptsFibronectin fibril assemblyTumor growthTumor microenvironmentNeuropilin-1Fibril assemblyStromal myofibroblastsNonreceptor tyrosine kinase c-AblTyrosine kinase c-AblHuman cancer specimensNew molecular mechanismCancer cell invasionNRP-1 levelsSerine 612Intracellular associationExtracellular domainMatrix stiffnessMolecular mechanismsC-AblGenetic depletionMatrix proteinsCell invasionClinical outcomesCancer specimensTherapeutic targetingAntibody neutralizationMechanical stress-activated integrin α5β1 induces opening of connexin 43 hemichannels
Batra N, Burra S, Siller-Jackson AJ, Gu S, Xia X, Weber GF, DeSimone D, Bonewald LF, Lafer EM, Sprague E, Schwartz MA, Jiang JX. Mechanical stress-activated integrin α5β1 induces opening of connexin 43 hemichannels. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 3359-3364. PMID: 22331870, PMCID: PMC3295295, DOI: 10.1073/pnas.1115967109.Peer-Reviewed Original ResearchMeSH KeywordsAndrostadienesAnimalsCell LineChromonesConnexin 43Extracellular Matrix ProteinsFibronectinsImmunomagnetic SeparationIntegrin alpha5beta1MiceMorpholinesOsteocytesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Interaction MappingRNA, Small InterferingStress, MechanicalWortmannin
2010
Spatiotemporal organization, regulation, and functions of tractions during neutrophil chemotaxis
Shin ME, He Y, Li D, Na S, Chowdhury F, Poh YC, Collin O, Su P, de Lanerolle P, Schwartz MA, Wang N, Wang F. Spatiotemporal organization, regulation, and functions of tractions during neutrophil chemotaxis. Blood 2010, 116: 3297-3310. PMID: 20616216, PMCID: PMC2995358, DOI: 10.1182/blood-2009-12-260851.Peer-Reviewed Original ResearchMeasuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics
Grashoff C, Hoffman BD, Brenner MD, Zhou R, Parsons M, Yang MT, McLean MA, Sligar SG, Chen CS, Ha T, Schwartz MA. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 2010, 466: 263-266. PMID: 20613844, PMCID: PMC2901888, DOI: 10.1038/nature09198.Peer-Reviewed Original ResearchConceptsFocal adhesionsFocal adhesion dynamicsMembrane cytoskeletal proteinsAdhesion dynamicsCell adhesion moleculeRegulatory mechanismsSpecific proteinsActin filamentsCell adhesionVinculinProteinMechanical tensionMechanical forcesRegulationPhysical forcesMolecular forcesAdhesionCellsVivoMechanotransductionPhysiologyNew biosensorFilamentsAbilityMigration
2007
A fluorescence resonance energy transfer activation sensor for Arf6
Hall B, McLean MA, Davis K, Casanova JE, Sligar SG, Schwartz MA. A fluorescence resonance energy transfer activation sensor for Arf6. Analytical Biochemistry 2007, 374: 243-249. PMID: 18162163, PMCID: PMC2277471, DOI: 10.1016/j.ab.2007.11.032.Peer-Reviewed Original ResearchConceptsMembrane targetingPlatelet-derived growth factorARF6 activationFluorescent proteinGreen fluorescent protein derivativesNormal membrane targetingRas family GTPasesDownstream effector proteinsSmall GTPase Arf6Small GTPase activationFluorescent reporter proteinFluorescent protein derivativesEffector proteinsExchange factorGTPase Arf6Effector domainReporter proteinGTPase activationRac activationN-terminusArf6Intact cellsCell migrationNormal regulationProtein
2006
Integrating Adhesion, Protrusion, and Contraction during Cell Migration
Schwartz MA, Horwitz AR. Integrating Adhesion, Protrusion, and Contraction during Cell Migration. Cell 2006, 125: 1223-1225. PMID: 16814706, DOI: 10.1016/j.cell.2006.06.015.Peer-Reviewed Original Research
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 kidneyZizimin2: a novel, DOCK180‐related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes
Nishikimi A, Meller N, Uekawa N, Isobe K, Schwartz MA, Maruyama M. Zizimin2: a novel, DOCK180‐related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes. FEBS Letters 2005, 579: 1039-1046. PMID: 15710388, DOI: 10.1016/j.febslet.2005.01.006.Peer-Reviewed Original ResearchAmino Acid SequenceAnimalsCdc42 GTP-Binding ProteinCell LineCloning, MolecularEnzyme ActivationGene Expression ProfilingGuanine Nucleotide Exchange FactorsLymphocytesMiceMolecular Sequence DataProtein BindingProtein IsoformsProtein Structure, TertiaryRac GTP-Binding ProteinsSequence AlignmentSubstrate Specificity
2004
Integrins Regulate Rac Targeting by Internalization of Membrane Domains
del Pozo MA, Alderson NB, Kiosses WB, Chiang HH, Anderson RG, Schwartz MA. Integrins Regulate Rac Targeting by Internalization of Membrane Domains. Science 2004, 303: 839-842. PMID: 14764880, DOI: 10.1126/science.1092571.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCell AdhesionCell LineCell MembraneCells, CulturedCholera ToxinCholesterolG(M1) GangliosideGlycosylphosphatidylinositolsGuanosine TriphosphateHumansIntegrin beta1IntegrinsLiposomesMembrane MicrodomainsMiceNIH 3T3 CellsRac1 GTP-Binding ProteinRatsRecombinant Fusion ProteinsSignal TransductionTransfectionConceptsMembrane domainsLipid raftsLipid raft markersPlasma membrane cholesterolCholesterol-rich membranesCell plasma membraneMembrane targetingAdhesion of cellsSmall GTPRaft markersIntegrin signalsPlasma membraneDownstream effectorsEffector activationMembrane lipidsMembrane cholesterolAnchorage-dependent cellsExtracellular matrixCell detachmentNonadherent cellsInternalizationRaftsCellsTargetingMembrane
2002
Effects of cell tension on the small GTPase Rac
Katsumi A, Milanini J, Kiosses WB, del Pozo MA, Kaunas R, Chien S, Hahn KM, Schwartz MA. Effects of cell tension on the small GTPase Rac. Journal Of Cell Biology 2002, 158: 153-164. PMID: 12105187, PMCID: PMC2173027, DOI: 10.1083/jcb.200201105.Peer-Reviewed Original ResearchMeSH KeywordsAmidesAnimalsAzepinesCell LineCell MembraneCell MovementCollagenDose-Response Relationship, DrugEnergy TransferGTP PhosphohydrolasesGuanine Nucleotide Exchange FactorsMicroscopy, FluorescenceMicroscopy, Phase-ContrastMicroscopy, VideoNaphthalenesNeoplasm ProteinsProteinsPseudopodiaPyridinesRac GTP-Binding ProteinsRatsStress, MechanicalTime FactorsT-Lymphoma Invasion and Metastasis-inducing Protein 1Transfection
2001
c-Abl Tyrosine Kinase Binds and Phosphorylates Phospholipid Scramblase 1*
Sun J, Zhao J, Schwartz M, Wang J, Wiedmer T, Sims P. c-Abl Tyrosine Kinase Binds and Phosphorylates Phospholipid Scramblase 1*. Journal Of Biological Chemistry 2001, 276: 28984-28990. PMID: 11390389, DOI: 10.1074/jbc.m102505200.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acid SubstitutionAnimalsBinding SitesCarrier ProteinsCell LineCells, CulturedFibroblastsGenes, ablGlutathione TransferaseHumansMembrane ProteinsMiceMice, KnockoutMutagenesis, Site-DirectedPhospholipid Transfer ProteinsPhospholipidsPhosphorylationProtein BindingProto-Oncogene Proteins c-ablRecombinant Fusion ProteinsRepetitive Sequences, Amino AcidSrc Homology DomainsTransfectionTyrosineConceptsPhospholipid scramblase 1SH3 domainC-AblAbl SH3 domainTyr phosphorylationMultiple proline-rich motifsScramblase 1Plasma membrane proteinsC-Abl bindsProline-rich motifDomain-binding siteProline-rich segmentDNA-damaging agent cisplatinC-Abl kinasePlasma membrane phospholipidsTandem repeat sequencesMutation of TyrCell linesCisplatin-induced phosphorylationKinase bindsGenotoxic stressMembrane proteinsDifferent SH3 domainsTransbilayer movementRepeat sequences
2000
Cell Adhesion Regulates Ubiquitin-mediated Degradation of the Platelet-derived Growth Factor Receptor β*
Baron V, Schwartz M. Cell Adhesion Regulates Ubiquitin-mediated Degradation of the Platelet-derived Growth Factor Receptor β*. Journal Of Biological Chemistry 2000, 275: 39318-39323. PMID: 11007771, DOI: 10.1074/jbc.m003618200.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsBlotting, WesternCell AdhesionCell DivisionCell LineCells, CulturedCysteine EndopeptidasesDose-Response Relationship, DrugDown-RegulationDynaminsEmbryo, MammalianEnzyme InhibitorsFibroblastsFibronectinsGTP PhosphohydrolasesHumansLigandsLysosomesMiceMultienzyme ComplexesPhosphorylationProteasome Endopeptidase ComplexProtein-Tyrosine KinasesReceptors, Platelet-Derived Growth FactorTemperatureTime FactorsTrypsinTyrphostinsUbiquitinsConceptsUbiquitin-dependent pathwayIntegrin-mediated adhesionPlatelet-derived growth factor receptor βPlatelet-derived growth factor receptor betaTyrosine kinase activityGrowth factor receptor βGrowth factor receptor betaProteasome pathwayDetachment of cellsReceptor autophosphorylationKinase activityCellular desensitizationPrimary fibroblastsExtracellular matrixCell detachmentAutophosphorylationProtein levelsCell linesPDGFGrowth factorReceptor betaReceptor βCellsPathwayRecent studiesDeath Effector Domain Protein PEA-15 Potentiates Ras Activation of Extracellular Signal Receptor-activated Kinase by an Adhesion-independent Mechanism
Ramos J, Hughes P, Renshaw M, Schwartz M, Formstecher E, Chneiweiss H, Ginsberg M. Death Effector Domain Protein PEA-15 Potentiates Ras Activation of Extracellular Signal Receptor-activated Kinase by an Adhesion-independent Mechanism. Molecular Biology Of The Cell 2000, 11: 2863-2872. PMID: 10982386, PMCID: PMC14961, DOI: 10.1091/mbc.11.9.2863.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsApoptosis Regulatory ProteinsCell AdhesionCell LineCHO CellsCricetinaeEnzyme ActivationGuanosine TriphosphateHumansIntracellular Signaling Peptides and ProteinsJNK Mitogen-Activated Protein KinasesMAP Kinase Kinase Kinase 1MiceMitogen-Activated Protein KinasesP38 Mitogen-Activated Protein KinasesPhosphoproteinsProtein Serine-Threonine KinasesRas ProteinsRecombinant Fusion ProteinsSignal TransductionConceptsPEA-15 expressionPEA-15ERK activationMitogen-activated protein kinase kinaseMitogen-activated protein kinase pathwayAdhesion-independent mechanismsRas-dependent mannerProtein kinase kinaseRegulation of apoptosisProtein kinase pathwayChinese hamster ovary cellsRas guanosineKinase kinaseRas activationSignal receptorHamster ovary cellsH-RasKinase pathwayERK activityIntegrin activationERK signalingAnchorage dependenceOncogenic processesOvary cellsApoptosisStimulation of Fascin Spikes by Thrombospondin-1 Is Mediated by the Gtpases Rac and Cdc42
Adams J, Schwartz M. Stimulation of Fascin Spikes by Thrombospondin-1 Is Mediated by the Gtpases Rac and Cdc42. Journal Of Cell Biology 2000, 150: 807-822. PMID: 10953005, PMCID: PMC2175285, DOI: 10.1083/jcb.150.4.807.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsActinsAnimalsBridged Bicyclo Compounds, HeterocyclicCarrier ProteinsCdc42 GTP-Binding ProteinCell AdhesionCell LineDepsipeptidesFibronectinsMiceMicrofilament ProteinsMuscle, SkeletalPeptides, CyclicRac GTP-Binding ProteinsRecombinant ProteinsStress, MechanicalThiazolesThiazolidinesThrombospondin 1TransfectionVinculinConceptsActin cytoskeletal organizationCytoskeletal organizationThrombospondin-1Matrix glycoprotein thrombospondin-1Actin-bundling protein fascinRho family GTPasesF-actin turnoverDominant-negative RacLocalization of fascinF-actin microspikesCell migration responseMotility of cellsGlycoprotein thrombospondin-1GTPases RacImportant physiological stimulusActive mutantComponent downstreamProtein fascinCdc42C2C12 myoblastsCell adhesionCell migrationBiochemical assaysExtracellular matrixProlonged activation