2023
TLN1 contains a cancer-associated cassette exon that alters talin-1 mechanosensitivity
Gallego-Paez L, Edwards W, Chanduri M, Guo Y, Koorman T, Lee C, Grexa N, Derksen P, Yan J, Schwartz M, Mauer J, Goult B. TLN1 contains a cancer-associated cassette exon that alters talin-1 mechanosensitivity. Journal Of Cell Biology 2023, 222: e202209010. PMID: 36880935, PMCID: PMC9997659, DOI: 10.1083/jcb.202209010.Peer-Reviewed Original ResearchConceptsExon 17bTerminal FERM domainVinculin bindingFERM domainSwitch domainAdhesion dynamicsCassette exonsSplicing analysisAdapter proteinTLN1Single isoformIsoform switchTalin-1Amino acidsFrame insertionExonsBiochemical analysisIsoformsProteinExon 17CytoskeletonGenesMechanotransductionDomainIntegrins
2021
Talin in mechanotransduction and mechanomemory at a glance
Goult BT, Brown NH, Schwartz MA. Talin in mechanotransduction and mechanomemory at a glance. Journal Of Cell Science 2021, 134: jcs258749. PMID: 34708856, PMCID: PMC8697387, DOI: 10.1242/jcs.258749.Peer-Reviewed Original ResearchConceptsHelical bundleHead domainC-terminal rod domainIntegrin conformational activationCytoskeletal linker proteinTerminal head domainExtracellular matrix proteinsCryptic binding sitesFlexible neck regionGlance articleAccompanying posterLinker proteinCytoplasmic tailConformational activationRod domainActin filamentsMatrix proteinsCell scienceTalinProteinBinding sitesDomain linksForce inducesDomainMechanotransduction
2012
Lessons from the endothelial junctional mechanosensory complex
Conway D, Schwartz MA. Lessons from the endothelial junctional mechanosensory complex. F1000 Biology Reports 2012, 4: 1. PMID: 22238515, PMCID: PMC3251317, DOI: 10.3410/b4-1.Peer-Reviewed Original Research
2011
Super-Resolution Microscopy: A New Dimension in Focal Adhesions
Schwartz MA. Super-Resolution Microscopy: A New Dimension in Focal Adhesions. Current Biology 2011, 21: r115-r116. PMID: 21300274, DOI: 10.1016/j.cub.2010.12.025.Peer-Reviewed Original Research
2010
Integrins and Extracellular Matrix in Mechanotransduction
Schwartz MA. Integrins and Extracellular Matrix in Mechanotransduction. Cold Spring Harbor Perspectives In Biology 2010, 2: a005066. PMID: 21084386, PMCID: PMC2982167, DOI: 10.1101/cshperspect.a005066.Peer-Reviewed Original ResearchConceptsIntegrin-mediated adhesionExtracellular matrixCytoskeletal linker proteinExtracellular matrix fibrilsIntracellular actin filamentsLinker proteinGenetic programActin filamentsExtracellular structuresCell survivalMatrix fibrilsIntegrinsCell functionCurrent knowledgeMechanotransductionMechanical forcesTransmits forcesIntracellularAdhesionCellsCytoskeletonProteinRegulationPathwayEnvironmental forcesMeasuring 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
2009
Rho GDP Dissociation Inhibitor 2 Suppresses Metastasis via Unconventional Regulation of RhoGTPases
Moissoglu K, McRoberts KS, Meier JA, Theodorescu D, Schwartz MA. Rho GDP Dissociation Inhibitor 2 Suppresses Metastasis via Unconventional Regulation of RhoGTPases. Cancer Research 2009, 69: 2838-2844. PMID: 19276387, PMCID: PMC2701105, DOI: 10.1158/0008-5472.can-08-1397.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCdc42 GTP-Binding ProteinCell AdhesionGuanine Nucleotide Dissociation InhibitorsHumansLung NeoplasmsMiceRac1 GTP-Binding ProteinRho GTP-Binding ProteinsRho Guanine Nucleotide Dissociation Inhibitor betaRho-Specific Guanine Nucleotide Dissociation InhibitorsRhoA GTP-Binding ProteinTumor Suppressor ProteinsUrinary Bladder NeoplasmsVinculinConceptsRho GTPasesFamily of proteinsGDP dissociation inhibitor 2Rho GDP dissociation inhibitor 2Dissociation inhibitor 2Membrane targetingMembrane associationPoint mutantsMetastasis suppressorRac1 activityGTPasesMetastasis suppressionInhibitor 2Suppress metastasisRhoGDI2ProteinSuppression correlatesRhoGDI1Weak inhibitorInhibitionRhoGTPasesMutantsMetastasis inhibitionStrong inhibitionSuppressor
2007
Function of the N-terminus of zizimin1: autoinhibition and membrane targeting
Meller N, Westbrook MJ, Shannon JD, Guda C, Schwartz MA. Function of the N-terminus of zizimin1: autoinhibition and membrane targeting. Biochemical Journal 2007, 409: 525-533. PMID: 17935486, PMCID: PMC2740492, DOI: 10.1042/bj20071263.Peer-Reviewed Original ResearchConceptsGEF domainCZH proteinsRho family small GTPasesPH domain bindsCdc42-specific GEFMultiple cellular functionsBasis of homologyN-terminal regionSmall GTPasesDomain bindsGEF activityRho proteinsCellular functionsRho-GEFsNovel functionN-terminusCritical regulatorStructural domainsLimited proteolysisZizimin1ProteinBindsDomainMembraneGTPasesA 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 regulationProteinMatrix‐specific PAK activation regulates vascular permeability in atherosclerosis
Orr A, Stockton R, Simmers M, Sanders J, Blackman B, Schwartz M. Matrix‐specific PAK activation regulates vascular permeability in atherosclerosis. The FASEB Journal 2007, 21: a268-a268. DOI: 10.1096/fasebj.21.5.a268-d.Peer-Reviewed Original ResearchPAK activationAtherosclerosis-prone regionsCell-cell junctionsActivation of PAKMembrane proteinsPAK phosphorylationBasement membrane proteinsPro-atherosclerotic cytokinesEndothelial permeabilityPAKActivationFibronectinSubendothelial monocytesVivoKinasePhosphorylationProteinP21Vascular permeabilityRecruitmentMatrix-specific p21-activated kinase activation regulates vascular permeability in atherogenesis
Orr AW, Stockton R, Simmers MB, Sanders JM, Sarembock IJ, Blackman BR, Schwartz MA. Matrix-specific p21-activated kinase activation regulates vascular permeability in atherogenesis. Journal Of Cell Biology 2007, 176: 719-727. PMID: 17312022, PMCID: PMC2064028, DOI: 10.1083/jcb.200609008.Peer-Reviewed Original ResearchConceptsP21-activated kinaseP21-activated kinase activationAtherosclerosis-prone regionsCell-cell junctionsBasement membrane proteinsMembrane proteinsPAK phosphorylationActivation of PAKKinase activationPAK activationEndothelial permeabilityFibronectinActivationSubendothelial monocytesVivoKinasePhosphorylationProteinVascular permeabilityAtherogenesisRecruitmentCells
2006
In Vivo Dynamics of Rac-Membrane Interactions
Moissoglu K, Slepchenko BM, Meller N, Horwitz AF, Schwartz MA. In Vivo Dynamics of Rac-Membrane Interactions. Molecular Biology Of The Cell 2006, 17: 2770-2779. PMID: 16597700, PMCID: PMC1474787, DOI: 10.1091/mbc.e06-01-0005.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsCell MembraneComputer SimulationDiffusionGenes, ReporterGuanine Nucleotide Dissociation InhibitorsKineticsMiceMicroscopy, ConfocalModels, TheoreticalPlasmidsProtein TransportRac GTP-Binding ProteinsRecombinant Fusion ProteinsRecombinant ProteinsRho-Specific Guanine Nucleotide Dissociation InhibitorsConceptsGuanine Nucleotide Dissociation InhibitorGTPase-activating proteinsGTP-RacNucleotide exchange factorsVivo dynamicsSmall hairpin RNADissociation inhibitorMembrane associationExchange factorRac functionGEF Tiam1Hairpin RNARhoGDIPhotobleaching methodRacCytosolOverexpressionMajor routeDissociation rate constantsTiam1RNAProteinDetectable rateMembraneActivation
2005
Integrin Activation and Matrix Binding Mediate Cellular Responses to Mechanical Stretch*
Katsumi A, Naoe T, Matsushita T, Kaibuchi K, Schwartz MA. Integrin Activation and Matrix Binding Mediate Cellular Responses to Mechanical Stretch*. Journal Of Biological Chemistry 2005, 280: 16546-16549. PMID: 15760908, DOI: 10.1074/jbc.c400455200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AdhesionEnzyme ActivationEnzyme InhibitorsExtracellular MatrixExtracellular Signal-Regulated MAP KinasesIntegrin alphaVbeta3IntegrinsJNK Mitogen-Activated Protein KinasesLigandsMAP Kinase Kinase 4MiceMitogen-Activated Protein Kinase KinasesNIH 3T3 CellsPhosphatidylinositol 3-KinasesPhosphorylationProtein ConformationSignal TransductionStress, MechanicalTime FactorsConceptsIntegrin activationExtracellular matrix proteinsRole of integrinsConformational activationBiochemical signalsNIH3T3 cellsMolecular mechanismsCellular responsesMatrix proteinsExtracellular matrixCell growthMechanical stretch stimulationIntegrin alphavbeta3IntegrinsMechanical tensionMechanical stretchCritical determinantStretch stimulationActivationPhosphoinositolMechanotransductionJNKProteinApoptosisDifferentiationRho 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
2004
The Novel Cdc42 Guanine Nucleotide Exchange Factor, Zizimin1, Dimerizes via the Cdc42-binding CZH2 Domain*
Meller N, Irani-Tehrani M, Ratnikov BI, Paschal BM, Schwartz MA. The Novel Cdc42 Guanine Nucleotide Exchange Factor, Zizimin1, Dimerizes via the Cdc42-binding CZH2 Domain*. Journal Of Biological Chemistry 2004, 279: 37470-37476. PMID: 15247287, DOI: 10.1074/jbc.m404535200.Peer-Reviewed Original ResearchConceptsExchange factorCdc42 Guanine Nucleotide Exchange FactorGuanine nucleotide exchange factorsRho family small GTPasesDomain-containing proteinsNucleotide exchange factorsMultiple cellular processesCDM proteinsCZH proteinsSmall GTPasesRho proteinsCellular processesCdc42 activationRho-GEFsCdc42Acid regionHomology analysisCritical regulatorZizimin1ProteinPositive cooperativityMutation analysisDimerizationDock180GTPases
2003
Rho-ROCK-LIMK-Cofilin Pathway Regulates Shear Stress Activation of Sterol Regulatory Element Binding Proteins
Lin T, Zeng L, Liu Y, DeFea K, Schwartz MA, Chien S, Shyy J. Rho-ROCK-LIMK-Cofilin Pathway Regulates Shear Stress Activation of Sterol Regulatory Element Binding Proteins. Circulation Research 2003, 92: 1296-1304. PMID: 12775580, DOI: 10.1161/01.res.0000078780.65824.8b.Peer-Reviewed Original ResearchMeSH KeywordsActin Depolymerizing FactorsActinsAnimalsCattleCCAAT-Enhancer-Binding ProteinsCell AdhesionCells, CulturedCHO CellsCricetinaeDNA-Binding ProteinsEndothelium, VascularHumansIntracellular Signaling Peptides and ProteinsLim KinasesLuciferasesMembrane ProteinsMicrofilament ProteinsMicroscopy, FluorescenceMutationPlasmidsProtein KinasesProtein Serine-Threonine KinasesProtein TransportProteinsRho GTP-Binding ProteinsRho-Associated KinasesSignal TransductionSterol Regulatory Element Binding Protein 1Sterol Regulatory Element Binding Protein 2Stress, MechanicalTranscription FactorsTransfectionConceptsSterol regulatory element-binding proteinLIMK-cofilin pathwayRegulatory element-binding proteinLIM kinaseElement-binding proteinRho-ROCKBinding proteinFluid shear stressSREBP cleavage-activating proteinSignal transduction pathwaysSmall GTPase RhoStress activationShear stress activationGolgi transportS2P proteasesTransduction pathwaysNegative mutantGTPase RhoSREBP activationIntegrin activationEndoplasmic reticulumEndothelial cell functionVascular endothelial cellsCaspase-3Protein
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 interactionCdc42Zizimin1RacActivatorGTPasesDomain
2000
Localized Rac Activation Dynamics Visualized in Living Cells
Kraynov V, Chamberlain C, Bokoch G, Schwartz M, Slabaugh S, Hahn K. Localized Rac Activation Dynamics Visualized in Living Cells. Science 2000, 290: 333-337. PMID: 11030651, DOI: 10.1126/science.290.5490.333.Peer-Reviewed Original ResearchConceptsSmall guanosine triphosphatasesSpatio-temporal controlMembrane rufflesGuanosine triphosphatasesSubcellular localizationNucleotide stateRac activationProtein activityDownstream targetsMotile cellsLiving cellsSpatial controlSpatio-temporal dynamicsGradient of activationCellsActivation dynamicsActivationRufflesTriphosphatasesPrecise spatial controlProteinRacLeading edgeApplicable approachLocalized effectDetermination of GTP loading on Rho
Ren X, Schwartz M. Determination of GTP loading on Rho. Methods In Enzymology 2000, 325: 264-272. PMID: 11036609, DOI: 10.1016/s0076-6879(00)25448-7.Peer-Reviewed Original ResearchConceptsRho-binding domainGTP-RhoLow molecular weight GTPaseAffinity precipitation assaysActin cytoskeleton organizationGTP loadingCytoskeleton organizationWeight GTPaseGTPase activityRho effectorCell lysatesGTPaseRhoPrecipitation assaysTRBDWestern immunoblottingDomainQuality controlPositive controlAssaysRhotekinEffectorsProtein