2023
Intracellular tension sensor reveals mechanical anisotropy of the actin cytoskeleton
Amiri S, Muresan C, Shang X, Huet-Calderwood C, Schwartz M, Calderwood D, Murrell M. Intracellular tension sensor reveals mechanical anisotropy of the actin cytoskeleton. Nature Communications 2023, 14: 8011. PMID: 38049429, PMCID: PMC10695988, DOI: 10.1038/s41467-023-43612-5.Peer-Reviewed Original ResearchConceptsF-actin architectureStress fibersCortical actinActin cytoskeletonMolecular tension sensorsF-actin stress fibersF-actin cytoskeletonFilamentous actin cytoskeletonMechanical forcesTension sensorCell divisionCytoskeletonCell migrationExtracellular matrixMyosin inhibitionActinDirection of stretchCellsCell axisUniaxial stretchStretchFRET
2015
Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization
Dubrac A, Genet G, Ola R, Zhang F, Pibouin-Fragner L, Han J, Zhang J, Thomas JL, Chedotal A, Schwartz MA, Eichmann A. Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization. Circulation 2015, 133: 409-421. PMID: 26659946, PMCID: PMC4729599, DOI: 10.1161/circulationaha.115.017537.Peer-Reviewed Original ResearchConceptsFront-rear polaritySprouting angiogenesisSignal integration mechanismImportant drug targetsNck adaptorsCytoskeletal dynamicsEndothelial cell migrationEmbryonic developmentAngiogenesis defectsPAK2 activationVessel sproutsNumber of diseasesBlood vessel growthDrug targetsCell migrationPostnatal retinaAngiogenic growthNckNck1AdaptorVessel growthKey processesEndothelial cellsPathological ocular neovascularizationInhibits neovascularizationZO-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 disruption
2011
Myosin II directly binds and inhibits Dbl family guanine nucleotide exchange factors
Lee C, Shin E, Hong J, Schwartz M, Kim E. Myosin II directly binds and inhibits Dbl family guanine nucleotide exchange factors. The FASEB Journal 2011, 25: 930.9-930.9. DOI: 10.1096/fasebj.25.1_supplement.930.9.Peer-Reviewed Original ResearchFocal complex formationDbl family guanineMyosin IIExchange factorFamily guanineATPase activityNonmuscle myosin IIComplex formationSpatiotemporal regulationGEF activityAdhesion dynamicsCdc42 GTPasesRho GTPasesCdc42 activationLamellipodial protrusionCell protrusionsActomyosin contractionGEFFunctional linkNIH3T3 fibroblastsCell migrationGTPasesCatalytic siteHomology modulesGuanineSrc and Caveolin-1 Reciprocally Regulate Metastasis via a Common Downstream Signaling Pathway in Bladder Cancer
Thomas S, Overdevest JB, Nitz MD, Williams PD, Owens CR, Sanchez-Carbayo M, Frierson HF, Schwartz MA, Theodorescu D. Src and Caveolin-1 Reciprocally Regulate Metastasis via a Common Downstream Signaling Pathway in Bladder Cancer. Cancer Research 2011, 71: 832-841. PMID: 21148751, PMCID: PMC4306590, DOI: 10.1158/0008-5472.can-10-0730.Peer-Reviewed Original ResearchConceptsActin stress fibersCav-1Active SrcStress fibersPhosphorylation of p190RhoGAPSrc protein levelsDownstream Signaling PathwaysCaveolin-1 expressionActivity of RhoACav-1 overexpressionTail vein inoculationRegulates MetastasisBladder cancerCommon downstreamHuman bladder cancer cellsPhosphorylated formSignaling pathwaysSrc levelsCell migrationBiochemical studiesLung metastasesMetastasis developmentSrc expressionBladder cancer cellsSrc
2010
Cell adhesion: integrating cytoskeletal dynamics and cellular tension
Parsons JT, Horwitz AR, Schwartz MA. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nature Reviews Molecular Cell Biology 2010, 11: 633-643. PMID: 20729930, PMCID: PMC2992881, DOI: 10.1038/nrm2957.Peer-Reviewed Original ResearchConceptsRho GTPasesGuanine nucleotide exchange factorsNucleotide exchange factorsGTPase-activating proteinsMyosin II activityActin-myosin contractionCytoskeletal dynamicsActin cytoskeletonCellular tensionExchange factorRho proteinsProtein TyrAdhesion dynamicsMorphogenetic processesCell rearAdhesion sizeCell frontIntegrin clusteringActin polymerizationRho activationMyosin IIDownstream signalingFeedback loopCell migrationComplex feedback loopsMyosin II directly binds and inhibits Dbl family guanine nucleotide exchange factors: a possible link to Rho family GTPases
Lee CS, Choi CK, Shin EY, Schwartz MA, Kim EG. Myosin II directly binds and inhibits Dbl family guanine nucleotide exchange factors: a possible link to Rho family GTPases. Journal Of Cell Biology 2010, 190: 663-674. PMID: 20713598, PMCID: PMC2928003, DOI: 10.1083/jcb.201003057.Peer-Reviewed Original ResearchMeSH KeywordsActomyosinAnimalsBinding SitesCdc42 GTP-Binding ProteinCell AdhesionCell MovementEnzyme ActivationGuanine Nucleotide Exchange FactorsHumansJurkat CellsMiceMyosin Type IINIH 3T3 CellsPlatelet-Derived Growth FactorProtein BindingRac1 GTP-Binding ProteinRatsRecombinant Fusion ProteinsRho GTP-Binding ProteinsRho Guanine Nucleotide Exchange FactorsRNA, Small InterferingConceptsFocal complex formationDbl family guanineMyosin IIExchange factorFamily guanineATPase activityNonmuscle myosin IIComplex formationGEF activitySpatiotemporal regulationRho familyCdc42 GTPasesAdhesion dynamicsRho GTPasesCdc42 activationLamellipodial protrusionCell protrusionsActomyosin contractionGEFNIH3T3 fibroblastsFunctional linkCell migrationGTPasesCatalytic siteHomology modules
2008
Endogenous RhoG is dispensable for integrin-mediated cell spreading but contributes to Rac-independent migration
Meller J, Vidali L, Schwartz MA. Endogenous RhoG is dispensable for integrin-mediated cell spreading but contributes to Rac-independent migration. Journal Of Cell Science 2008, 121: 1981-1989. PMID: 18505794, PMCID: PMC2759683, DOI: 10.1242/jcs.025130.Peer-Reviewed Original Research
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 regulationProteinBlocking p21-activated Kinase Reduces Lipopolysaccharide-induced Acute Lung Injury by Preventing Polymorphonuclear Leukocyte Infiltration
Reutershan J, Stockton R, Zarbock A, Sullivan GW, Chang D, Scott D, Schwartz MA, Ley K. Blocking p21-activated Kinase Reduces Lipopolysaccharide-induced Acute Lung Injury by Preventing Polymorphonuclear Leukocyte Infiltration. American Journal Of Respiratory And Critical Care Medicine 2007, 175: 1027-1035. PMID: 17322107, PMCID: PMC1899271, DOI: 10.1164/rccm.200612-1822oc.Peer-Reviewed Original ResearchConceptsAcute lung injuryLung injuryPMN migrationPolymorphonuclear leukocytesAlveolar spaceLipopolysaccharide-induced lung injuryMurine lung injuryPolymorphonuclear leukocyte infiltrationLeukocyte-endothelial interactionsAlveolo-capillary membraneOxidative burstRole of PAKsLeukocyte infiltrationChemokine receptorsLung interstitiumMurine modelExcessive recruitmentPMN chemoattractantInjuryCytoskeletal actin polymerizationAdhesion moleculesCritical mediatorCell migrationAttractive targetPAK phosphorylation
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
Rho Proteins in Cell Migration and Metastasis
Titus B, Schwartz MA, Theodorescu D. Rho Proteins in Cell Migration and Metastasis. Critical Reviews In Eukaryotic Gene Expression 2005, 15: 103-114. DOI: 10.1615/critreveukargeneexpr.v15.i2.20.Peer-Reviewed Original ResearchRho Proteins in Cell Migration and Metastasis
Titus B, Schwartz M, Theodorescu D. Rho Proteins in Cell Migration and Metastasis. Critical Reviews In Eukaryotic Gene Expression 2005, 15: 103-114. PMID: 16022631, DOI: 10.1615/critreveukaryotgeneexpr.v15.i2.20.Peer-Reviewed Original Research
2003
Cell Migration: Integrating Signals from Front to Back
Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, Parsons JT, Horwitz AR. Cell Migration: Integrating Signals from Front to Back. Science 2003, 302: 1704-1709. PMID: 14657486, DOI: 10.1126/science.1092053.Peer-Reviewed Original ResearchModulation of Rac Localization and Function by Dynamin
Schlunck G, Damke H, Kiosses WB, Rusk N, Symons MH, Waterman-Storer CM, Schmid SL, Schwartz MA. Modulation of Rac Localization and Function by Dynamin. Molecular Biology Of The Cell 2003, 15: 256-267. PMID: 14617821, PMCID: PMC307545, DOI: 10.1091/mbc.e03-01-0019.Peer-Reviewed Original ResearchConceptsLamellipodia formationDorsal rufflesRac activityCell spreadingFluorescence resonance energy transfer (FRET) imagingFormation of lamellipodiaFormation of phagosomesGTPase dynaminFocal complexesSmall GTPasesRho familyEndocytic pathwayDynaminCell adhesionCell migrationRufflesRacLamellipodiaPredominant localizationIndispensable roleLocalizationK44AGTPasesMacropinosomesInvadopodia
2002
Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins
Meller N, Irani-Tehrani M, Kiosses WB, Del Pozo MA, Schwartz MA. Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins. Nature Cell Biology 2002, 4: 639-647. PMID: 12172552, DOI: 10.1038/ncb835.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SequenceAnimalsBinding SitesCdc42 GTP-Binding ProteinCloning, MolecularEnzyme ActivationGuanine Nucleotide Exchange FactorsHumansMiceMolecular Sequence DataProtein Structure, TertiaryRho GTP-Binding ProteinsRNA, MessengerSequence Homology, Amino AcidTissue DistributionConceptsGuanine nucleotide exchange factorsCdc42 activatorGEF domainRho family GTPases RacNucleotide exchange factorsCDM proteinsRho proteinsRho familyGTPases RacNew superfamilySequence comparisonCdc42 activationNew proteinsMutational analysisGene expressionBiochemical searchCell migrationProteinDirect interactionCdc42Zizimin1RacActivatorGTPasesDomainA Fragment of Paxillin Binds the α4Integrin Cytoplasmic Domain (Tail) and Selectively Inhibits α4-Mediated Cell Migration*
Liu S, Kiosses WB, Rose DM, Slepak M, Salgia R, Griffin JD, Turner CE, Schwartz MA, Ginsberg MH. A Fragment of Paxillin Binds the α4Integrin Cytoplasmic Domain (Tail) and Selectively Inhibits α4-Mediated Cell Migration*. Journal Of Biological Chemistry 2002, 277: 20887-20894. PMID: 11919182, DOI: 10.1074/jbc.m110928200.Peer-Reviewed Original ResearchConceptsCytoplasmic domainPaxillin interactionCell migrationIntegrin-mediated cell adhesionIntegrin alpha subunitsEnhanced cell migrationPaxillin bindingFunctional responseFocal adhesionsCellular functionsPaxillinCardiac developmentAlanine substitutionsMutational analysisAdaptor moleculeAcid regionAlpha subunitBiological processesCell spreadingCellular responsesCell adhesionIntegrin subunitsSubunitsTernary complexFragments
2001
Increased filamin binding to β-integrin cytoplasmic domains inhibits cell migration
Calderwood D, Huttenlocher A, Kiosses W, Rose D, Woodside D, Schwartz M, Ginsberg M. Increased filamin binding to β-integrin cytoplasmic domains inhibits cell migration. Nature Cell Biology 2001, 3: 1060-1068. PMID: 11781567, DOI: 10.1038/ncb1201-1060.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsBinding SitesCell MovementCell PolarityCHO CellsContractile ProteinsCricetinaeCytoplasmCytoskeletonFibronectinsFilaminsFocal AdhesionsHumansIntegrin beta ChainsIntegrinsIsoleucineJurkat CellsMicrofilament ProteinsProtein Structure, TertiaryRecombinant Fusion ProteinsTalinValineConceptsFocal adhesion formationFilamin bindingCell migrationMembrane protrusionsMatrix assemblyIntegrin-dependent cell migrationFibronectin matrix assemblyAmino acid substitutionsInhibits cell migrationAnimal developmentActin cytoskeletonIntegrin tailsBiochemical signalsAdhesion receptorsFilaminCell polarizationTalinAcid substitutionsExtracellular matrixAdhesion formationTailBindingAssemblyMigrationSelective loss
2000
Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover
Ren X, Kiosses W, Sieg D, Otey C, Schlaepfer D, Schwartz M. Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover. Journal Of Cell Science 2000, 113: 3673-3678. PMID: 11017882, DOI: 10.1242/jcs.113.20.3673.Peer-Reviewed Original ResearchStimulation 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