2023
Altered Integrin Signaling in Thoracic Aortopathy
Humphrey J, Schwartz M. Altered Integrin Signaling in Thoracic Aortopathy. Arteriosclerosis Thrombosis And Vascular Biology 2023, 43: 1154-1156. PMID: 37165879, DOI: 10.1161/atvbaha.123.319404.Commentaries, Editorials and Letters
2022
Integrin Conformational Dynamics and Mechanotransduction
Kolasangiani R, Bidone T, Schwartz M. Integrin Conformational Dynamics and Mechanotransduction. Cells 2022, 11: 3584. PMID: 36429013, PMCID: PMC9688440, DOI: 10.3390/cells11223584.Peer-Reviewed Original ResearchConceptsCell-cell adhesionCell-extracellular matrixExtracellular ligandsIntegrin affinityConformational dynamicsIntegrin familyConformational statesConformational transitionTissue integrityCell functionCentral mediatorRemarkable convergenceMechanical forcesForce transmissionCytoskeletonMechanotransductionAdhesionFirm adhesionUnanswered questionsIntegrinsNew informationPathwayLigands
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 ResearchMeSH KeywordsBinding SitesIntegrinsMechanotransduction, CellularProtein BindingSignal TransductionTalinConceptsHelical 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 inducesDomainMechanotransductionIntegrin-based mechanosensing through conformational deformation
Driscoll TP, Bidone TC, Ahn SJ, Yu A, Groisman A, Voth GA, Schwartz MA. Integrin-based mechanosensing through conformational deformation. Biophysical Journal 2021, 120: 4349-4359. PMID: 34509509, PMCID: PMC8553792, DOI: 10.1016/j.bpj.2021.09.010.Peer-Reviewed Original ResearchMeSH KeywordsCell AdhesionIntegrin alphaVbeta3IntegrinsLigandsMechanical PhenomenaProtein BindingTalinConceptsCellular mechanosensingFocal adhesion kinase activationIntegrin conformational activationLarge-scale conformational transitionsWild-type integrinIntegrin mutantsEmbryonic developmentConformational activationCellular stiffnessHigh-affinity stateKinase activationSubstrate stiffnessBiological processesIntegrin activationCell spreadingMutantsIntegrin conformationTraction stressConformational deformationConformational transitionIntegrinsMechanosensingSoluble ligandsAffinity stateMolecular-level information
2020
Actin flow-dependent and -independent force transmission through integrins
Driscoll TP, Ahn SJ, Huang B, Kumar A, Schwartz MA. Actin flow-dependent and -independent force transmission through integrins. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 32413-32422. PMID: 33262280, PMCID: PMC7768777, DOI: 10.1073/pnas.2010292117.Peer-Reviewed Original ResearchConceptsActin binding siteProtein interactionsDistinct protein interactionsDynamic protein interactionsIntegrin-dependent adhesionBinding sitesSubstrate stiffnessActin flowActin filamentsStiff substratesExtracellular matrixTalinVinculinIntegrinsReciprocal exchangeClutchesForce transmissionAdhesionFlow-independent mechanismsLarge adhesionABS3Cell edgeABS2SitesInteractionIntegrin-mediated adhesions in regulation of cellular senescence
Shin EY, Park JH, You ST, Lee CS, Won SY, Park JJ, Kim HB, Shim J, Soung NK, Lee OJ, Schwartz MA, Kim EG. Integrin-mediated adhesions in regulation of cellular senescence. Science Advances 2020, 6: eaay3909. PMID: 32494696, PMCID: PMC7202880, DOI: 10.1126/sciadv.aay3909.Peer-Reviewed Original ResearchConceptsClathrin-mediated endocytosisCellular senescenceG protein-coupled receptor kinasesProtein-coupled receptor kinasesElevated reactive oxygen species (ROS) productionIntegrin-mediated adhesionIntegrin endocytosisAmphiphysin 1Exchange factorReactive oxygen species productionReceptor kinaseOxygen species productionMolecular mechanismsCalpain cleavageSenescenceCell adhesionDirect competitionHuman fibroblastsGIT levelsSpecies productionΒPixNew therapeutic directionIntegrinsEndocytosisCentral role
2019
Coarse-Grained Simulation of Full-Length Integrin Activation
Bidone TC, Polley A, Jin J, Driscoll T, Iwamoto DV, Calderwood DA, Schwartz MA, Voth GA. Coarse-Grained Simulation of Full-Length Integrin Activation. Biophysical Journal 2019, 116: 1000-1010. PMID: 30851876, PMCID: PMC6428961, DOI: 10.1016/j.bpj.2019.02.011.Peer-Reviewed Original Research
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
2014
Integrin adjunct therapy for melanoma
Andarawewa KL, Moissoglu K, Lee C, Ando Y, Yu M, Debnath P, Shannon JD, Sirinivasan S, Conaway MR, Weber MJ, Schwartz MA. Integrin adjunct therapy for melanoma. Pigment Cell & Melanoma Research 2014, 28: 114-116. PMID: 25264294, PMCID: PMC6542633, DOI: 10.1111/pcmr.12320.Peer-Reviewed Original ResearchMechanotransduction and extracellular matrix homeostasis
Humphrey JD, Dufresne ER, Schwartz MA. Mechanotransduction and extracellular matrix homeostasis. Nature Reviews Molecular Cell Biology 2014, 15: 802-812. PMID: 25355505, PMCID: PMC4513363, DOI: 10.1038/nrm3896.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytoskeletonExtracellular MatrixHomeostasisHumansIntegrinsMechanotransduction, CellularSticking to it: Tracking the paths of integrin signalling
Schwartz M. Sticking to it: Tracking the paths of integrin signalling. Nature Cell Biology 2014, 16: 487-487. PMID: 24875734, DOI: 10.1038/ncb2971.Peer-Reviewed Original Research
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 workN-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
2011
JNK2 Promotes Endothelial Cell Alignment under Flow
Hahn C, Wang C, Orr AW, Coon BG, Schwartz MA. JNK2 Promotes Endothelial Cell Alignment under Flow. PLOS ONE 2011, 6: e24338. PMID: 21909388, PMCID: PMC3164210, DOI: 10.1371/journal.pone.0024338.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinase c-Jun N-terminal kinaseProtein kinase c-Jun N-terminal kinaseC-Jun N-terminal kinaseActin stress fibersN-terminal kinaseFocal adhesionsBasement membrane proteinsMembrane proteinsLaminar shear stressStress fibersGene expressionJNK activityIntegrin activationJNK2 activationEndothelial cell alignmentJNK activationActivated JNKExtracellular matrixInflammatory gene expressionCell alignmentUnexpected connectionEndothelial cellsActivationPathwayCellsEffects of integrin-mediated cell adhesion on plasma membrane lipid raft components and signaling
Norambuena A, Schwartz MA. Effects of integrin-mediated cell adhesion on plasma membrane lipid raft components and signaling. Molecular Biology Of The Cell 2011, 22: 3456-3464. PMID: 21795400, PMCID: PMC3172269, DOI: 10.1091/mbc.e11-04-0361.Peer-Reviewed Original ResearchConceptsLipid raft componentsRaft componentsLipid raftsCyclic adenosine monophosphateCell detachmentCell adhesionLipid raft markersGlycosylphosphatidylinositol-linked proteinsRaft associationRaft markersRho GTPasesNonraft fractionsDetachment of cellsElevation of cAMPStudy of integrinsTermination of growthPlasma membraneH-RasAnchorage dependenceKey defenseCell growthFlotillin2Sucrose gradientsCancer metastasisLipid tailsSuper-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 forcesMatrix-Specific Protein Kinase A Signaling Regulates p21-Activated Kinase Activation by Flow in Endothelial Cells
Funk SD, Yurdagul A, Green JM, Jhaveri KA, Schwartz MA, Orr AW. Matrix-Specific Protein Kinase A Signaling Regulates p21-Activated Kinase Activation by Flow in Endothelial Cells. Circulation Research 2010, 106: 1394-1403. PMID: 20224042, PMCID: PMC2862370, DOI: 10.1161/circresaha.109.210286.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsBasement MembraneCattleCdc42 GTP-Binding ProteinCells, CulturedCyclic AMP-Dependent Protein KinasesEndothelial CellsEnzyme ActivationEnzyme ActivatorsHumansIloprostInflammationInflammation MediatorsInjections, IntraperitonealIntegrinsMaleMechanotransduction, CellularMiceMice, Inbred C57BLNF-kappa BP21-Activated KinasesPhosphorylationProtein Kinase InhibitorsPulsatile FlowRac GTP-Binding ProteinsRegional Blood FlowStress, MechanicalTime FactorsTransfectionConceptsInflammatory gene expressionNF-kappaB activationInflammatory signalingEndothelial cellsProstacyclin analogue iloprostBasement membrane proteinsBlood flow patternsPKA-dependent inhibitionInflammatory pathwaysAnalogue iloprostGene expressionKappaB activationNF-kappaB.Subendothelial extracellular matrixNuclear factorPAK activationBasement membraneRemembrance of Dead Cells Past: Discovering That the Extracellular Matrix Is a Cell Survival Factor
Schwartz MA. Remembrance of Dead Cells Past: Discovering That the Extracellular Matrix Is a Cell Survival Factor. Molecular Biology Of The Cell 2010, 21: 499-500. PMID: 20150528, PMCID: PMC2820415, DOI: 10.1091/mbc.e09-07-0602.Peer-Reviewed Original Research
2009
RalA-Exocyst Complex Regulates Integrin-Dependent Membrane Raft Exocytosis and Growth Signaling
Balasubramanian N, Meier JA, Scott DW, Norambuena A, White MA, Schwartz MA. RalA-Exocyst Complex Regulates Integrin-Dependent Membrane Raft Exocytosis and Growth Signaling. Current Biology 2009, 20: 75-79. PMID: 20005108, PMCID: PMC2822103, DOI: 10.1016/j.cub.2009.11.016.Peer-Reviewed Original ResearchConceptsPlasma membraneRecycling endosomesGrowth signalingActivation of Arf6Small GTPase RalACaveolin-dependent internalizationLipid raft microdomainsAnchorage-independent growthEffects of integrinsExocyst complexActive RalARaft microdomainsMembrane raftsRaft markersIntegrin signalingPancreatic cancer cellsRalAAnchorage dependenceAnchorage independenceCell growthSignalingCell detachmentCancer cellsEndosomesExocytosis