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
2019
Filamin A mediates isotropic distribution of applied force across the actin network
Kumar A, Shutova MS, Tanaka K, Iwamoto DV, Calderwood DA, Svitkina TM, Schwartz MA. Filamin A mediates isotropic distribution of applied force across the actin network. Journal Of Cell Biology 2019, 218: 2481-2491. PMID: 31315944, PMCID: PMC6683746, DOI: 10.1083/jcb.201901086.Peer-Reviewed Original ResearchConceptsTalin tension sensorStress fibersActin networkFilamin ACortical actin networkCortical actin filamentsIntegrin-mediated adhesionActin cytoskeletonFocal adhesionsCortical actinFLNA knockdownActin filamentsTalinKnockdownCell sensingDirection of stretchTension sensorPhysiology of muscleUniaxial stretchForce transmissionCytoskeletonStrainsStretchAdhesionReexpressionMKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation
Hu X, Liu ZZ, Chen X, Schulz VP, Kumar A, Hartman AA, Weinstein J, Johnston JF, Rodriguez EC, Eastman AE, Cheng J, Min L, Zhong M, Carroll C, Gallagher PG, Lu J, Schwartz M, King MC, Krause DS, Guo S. MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation. Nature Communications 2019, 10: 1695. PMID: 30979898, PMCID: PMC6461646, DOI: 10.1038/s41467-019-09636-6.Peer-Reviewed Original ResearchConceptsCell fate reprogrammingChromatin accessibilityActin cytoskeletonSomatic cell reprogrammingPluripotency transcription factorsGlobal chromatin accessibilityGenomic accessibilityCytoskeleton (LINC) complexCell reprogrammingCytoskeletal genesTranscription factorsReprogrammingPluripotencyChromatinCytoskeletonMKL1Unappreciated aspectPathwayNuclear volumeNucleoskeletonSUN2CellsActivationGenesExpression
2018
Talin as a mechanosensitive signaling hub
Goult BT, Yan J, Schwartz MA. Talin as a mechanosensitive signaling hub. Journal Of Cell Biology 2018, 217: 3776-3784. PMID: 30254032, PMCID: PMC6219721, DOI: 10.1083/jcb.201808061.Peer-Reviewed Original ResearchConceptsSignaling hubsExtracellular matrixRod domainTalin rod domainIntegrin β subunitsDifferent protein interactionsLong rod domainSwitch-like behaviorActin cytoskeletonCytoplasmic domainCytoplasmic proteinsProtein interactionsHelical bundleGlobular head domainTalin functionTransmembrane receptorsHelix bundleΒ-subunitHead domainIntegrin familyTalinCell adhesionIndividual domainsRecent evidenceDomain
2013
Integrins in mechanotransduction
Ross TD, Coon BG, Yun S, Baeyens N, Tanaka K, Ouyang M, Schwartz MA. Integrins in mechanotransduction. Current Opinion In Cell Biology 2013, 25: 613-618. PMID: 23797029, PMCID: PMC3757118, DOI: 10.1016/j.ceb.2013.05.006.Peer-Reviewed Original ResearchConceptsMolecular mechanismsIntegrin-mediated adhesionImportant regulatory eventActin cytoskeletonRegulatory eventsExtracellular matrixNormal physiologyCell functionMajor insightsCentral roleCellsRecent advancesCytoskeletonEffect of forceMechanotransductionAdhesionIntegrinsPathwayPhysiologyMechanismRecent work
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 loops
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
The Molecular Adapter SLP-76 Relays Signals from Platelet Integrin αIIbβ3 to the Actin Cytoskeleton*
Obergfell A, Judd B, del Pozo M, Schwartz M, Koretzky G, Shattil S. The Molecular Adapter SLP-76 Relays Signals from Platelet Integrin αIIbβ3 to the Actin Cytoskeleton*. Journal Of Biological Chemistry 2000, 276: 5916-5923. PMID: 11113155, DOI: 10.1074/jbc.m010639200.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdaptor Proteins, Signal TransducingAnimalsBlood PlateletsCell AdhesionCell Cycle ProteinsCHO CellsCricetinaeCytoskeletonEnzyme PrecursorsFibrinogenHumansIntracellular Signaling Peptides and ProteinsPhosphoproteinsPhosphorylationPlatelet Glycoprotein GPIIb-IIIa ComplexProtein BindingProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-vavPseudopodiaRac GTP-Binding ProteinsSignal TransductionSyk KinaseConceptsSLP-76SLAP-130Lamellipodia formationSLP-76 functionAdhesion-dependent activationCHO cell adhesionCell expression systemSLP-76 phosphorylationChinese hamster ovary cell expression systemSLP-76 expressionSyk tyrosine kinasePlatelet integrin αIIbβ3Sites of adhesionRac effectorPAK kinasesActin cytoskeletonAdherent CHO cellsExchange factorActin rearrangementCytoskeletal reorganizationActin reorganizationTyrosine phosphorylationExpression systemCell spreadingTyrosine kinase
1998
Regulation of inositol lipid kinases by Rho and Rac
Ren X, Schwartz M. Regulation of inositol lipid kinases by Rho and Rac. Current Opinion In Genetics & Development 1998, 8: 63-67. PMID: 9529607, DOI: 10.1016/s0959-437x(98)80063-4.Peer-Reviewed Original Research
1995
Mapping in vivo associations of cytoplasmic proteins with integrin beta 1 cytoplasmic domain mutants.
Lewis J, Schwartz M. Mapping in vivo associations of cytoplasmic proteins with integrin beta 1 cytoplasmic domain mutants. Molecular Biology Of The Cell 1995, 6: 151-160. PMID: 7540435, PMCID: PMC275825, DOI: 10.1091/mbc.6.2.151.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsActininAmino Acid SequenceAnimalsBinding SitesCell Adhesion MoleculesChickensCytoplasmCytoskeletal ProteinsFluorescent Antibody TechniqueFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesIntegrin beta1IntegrinsMacromolecular SubstancesMiceMolecular Sequence DataMutagenesisProtein-Tyrosine KinasesRecombinant ProteinsSequence DeletionTalinVinculinConceptsFocal adhesion kinaseBeta 1 integrinC-terminusCytoplasmic proteinsF-actinMutant beta 1Entire cytoplasmic domainCytoplasmic domain mutantsSpecific cytoskeletal proteinsBeta 1Wild-type integrinCultured mouse fibroblastsBeta 1 integrin subunitActin cytoskeletonFocal adhesionsCytoplasmic domainDomain mutantsAdhesion kinaseAlpha-actininTrigger intracellularVivo associationCytoskeletal proteinsTalinFocal contactsAmino acids
1994
The small GTP-binding protein Rho regulates a phosphatidylinositol 4-phosphate 5-kinase in mammalian cells
Chong L, Traynor-Kaplan A, Bokoch G, Schwartz M. The small GTP-binding protein Rho regulates a phosphatidylinositol 4-phosphate 5-kinase in mammalian cells. Cell 1994, 79: 507-513. PMID: 7954816, DOI: 10.1016/0092-8674(94)90259-3.Peer-Reviewed Original ResearchMeSH KeywordsADP Ribose TransferasesAnimalsBotulinum ToxinsCalciumCell AdhesionCells, CulturedDrosophila ProteinsFibroblastsGTP-Binding ProteinsGuanosine 5'-O-(3-Thiotriphosphate)IntegrinsLovastatinMembrane ProteinsMiceMicroinjectionsPhosphatidylinositol 4,5-DiphosphatePhosphatidylinositol PhosphatesPhosphotransferases (Alcohol Group Acceptor)Platelet-Derived Growth FactorRecombinant ProteinsSignal TransductionThrombinConceptsPlatelet-derived growth factorBotulinum C3 exoenzymeSmall GTPPIP2 synthesisC3 exoenzymePIP2 hydrolysisProduction of phosphatidylinositolIntegrin-mediated adhesionEffects of RhoTreatment of cellsCalcium mobilizationActin cytoskeletonDiminished calcium mobilizationMammalian cellsProtein RhoPIP2 levelsCell lysatesGTP gamma SGTPRhoPhosphatidylinositolExoenzymeGamma SGrowth factorNonadherent cellsDiffering structural requirements for GTPase-activating protein responsiveness and NADPH oxidase activation by Rac.
Xu X, Barry D, Settleman J, Schwartz M, Bokoch G. Differing structural requirements for GTPase-activating protein responsiveness and NADPH oxidase activation by Rac. Journal Of Biological Chemistry 1994, 269: 23569-23574. PMID: 8089125, DOI: 10.1016/s0021-9258(17)31553-3.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBinding, CompetitiveDNA PrimersEnzyme ActivationGTP-Binding ProteinsGTPase-Activating ProteinsIn Vitro TechniquesMolecular Sequence DataNADH, NADPH OxidoreductasesNADPH OxidasesProteinsRac GTP-Binding ProteinsRas GTPase-Activating ProteinsRecombinant ProteinsStructure-Activity RelationshipConceptsGTPase-activating proteinsEffector domainFunction of RacGTP/GDP stateInteraction of RasDouble mutationNADPH oxidase activationGAP bindingActin cytoskeletonMembrane rufflingActin assemblyOxidase activationGTP hydrolysisRac-GTPGDP stateWild typeSuperoxide-forming NADPH oxidaseInteraction sitesProtein responsivenessProteinResidues 12MutationsRacRac2Phagocytic leukocytes