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
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
Integrin-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 ResearchConceptsCellular 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
2016
Force 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 probePhagocytosisMembraneAngiogenesisFunction
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
2012
Mechanical 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
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 forces
2008
Cell adhesion receptors in mechanotransduction
Schwartz MA, DeSimone DW. Cell adhesion receptors in mechanotransduction. Current Opinion In Cell Biology 2008, 20: 551-556. PMID: 18583124, PMCID: PMC2581799, DOI: 10.1016/j.ceb.2008.05.005.Peer-Reviewed Original ResearchConceptsAdhesion receptorsCell fate decisionsCadherin-mediated adhesionCell adhesion receptorsFate decisionsMorphogenetic movementsTissue-level responsesCultured cellsExtracellular matrixMechanotransductionLevel responseCellsCytoskeletonCadherinReceptorsOrganismsAdhesionIntegrinsPathwayMechanical stimulationIntracellularMechanismMechanical stressResponseCentral mechanisms
2007
Rac, membrane heterogeneity, caveolin and regulation of growth by integrins
Del Pozo MA, Schwartz MA. Rac, membrane heterogeneity, caveolin and regulation of growth by integrins. Trends In Cell Biology 2007, 17: 246-250. PMID: 17363257, DOI: 10.1016/j.tcb.2007.03.001.Peer-Reviewed Original ResearchConceptsCholesterol-enriched membrane domainsAnchorage dependenceGrowth regulatory pathwaysRegulation of growthBlocks cell proliferationCancer cell invasionMembrane domainsRegulatory pathwaysCaveolin-1Cell invasionTyr-14Membrane heterogeneityNon-adherent cellsMultiple pathwaysCell proliferationBinding sitesRacImportant mechanismIntegrinsPathwayCaveolinCellsPtdInsCaveolaeEndocytosis
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 stimulationActivationPhosphoinositolMechanotransductionJNKProteinApoptosisDifferentiation
2001
Integrin signaling revisited
Schwartz M. Integrin signaling revisited. Trends In Cell Biology 2001, 11: 466-470. PMID: 11719050, DOI: 10.1016/s0962-8924(01)02152-3.Peer-Reviewed Original ResearchIntegrins and cell proliferationregulation of cyclin-dependent kinases via cytoplasmic signaling pathways
Schwartz M, Assoian R. Integrins and cell proliferationregulation of cyclin-dependent kinases via cytoplasmic signaling pathways. Journal Of Cell Science 2001, 114: 2553-2560. PMID: 11683383, DOI: 10.1242/jcs.114.14.2553.Peer-Reviewed Original ResearchConceptsCyclin-dependent kinasesG1 phase cyclin-dependent kinasesPhase cyclin-dependent kinasesCell cycle progressionCycle progressionCytoplasmic signaling pathwaysIntegrin-dependent signalsMammalian cellsGrowth factor receptorSignaling pathwaysERK pathwayCell adhesionExtracellular matrixDiverse arrayFactor receptorCyclin D1KinaseRegulationPathwayGrowth factorIntegrinsRecent advancesIntegrated controlReceptorsAdhesionCoordinate signaling by integrins and receptor tyrosine kinases in the regulation of G1 phase cell-cycle progression
Assoian R, Schwartz M. Coordinate signaling by integrins and receptor tyrosine kinases in the regulation of G1 phase cell-cycle progression. Current Opinion In Genetics & Development 2001, 11: 48-53. PMID: 11163150, DOI: 10.1016/s0959-437x(00)00155-6.Peer-Reviewed Original ResearchConceptsCell cycle progressionReceptor tyrosine kinasesG1 phase cyclinsDependent kinasesTyrosine kinasePhase cell cycle progressionG1 phase cell cycle progressionExtracellular matrix proteinsSoluble growth factorsRho GTPasesGrowth factor receptorRegulated signalingMatrix proteinsKinaseG1 phaseCell proliferationIntegrinsCyclinGrowth factorRecent studiesGTPasesActivationReceptorsSignalingERK
1998
Integrins Regulate the Association and Phosphorylation of Paxillin by c-Abl*
Lewis J, Schwartz M. Integrins Regulate the Association and Phosphorylation of Paxillin by c-Abl*. Journal Of Biological Chemistry 1998, 273: 14225-14230. PMID: 9603926, DOI: 10.1074/jbc.273.23.14225.Peer-Reviewed Original ResearchConceptsC-AblCell adhesionTyrosine kinaseFocal adhesion protein paxillinNon-receptor tyrosine kinasePhosphorylation of paxillinC-Abl kinaseEffects of integrinsFocal adhesionsProtein paxillinIntegrin regulationPaxillinTransient recruitmentKinaseIntegrinsCell functionProteinAdhesionPhosphorylationTyrosineRegulationABLRecruitmentActivationLocalization
1997
Integrins, adhesion and apoptosis
Meredith J, Schwartz M. Integrins, adhesion and apoptosis. Trends In Cell Biology 1997, 7: 146-150. PMID: 17708932, DOI: 10.1016/s0962-8924(97)01002-7.Peer-Reviewed Original Research
1995
Integrins: Emerging Paradigms of Signal Transduction
Schwartz M, Schaller M, Ginsberg M. Integrins: Emerging Paradigms of Signal Transduction. Annual Review Of Cell And Developmental Biology 1995, 11: 549-599. PMID: 8689569, DOI: 10.1146/annurev.cb.11.110195.003001.Peer-Reviewed Original Research
1994
Integrating with integrins.
Schwartz M, Ingber D. Integrating with integrins. Molecular Biology Of The Cell 1994, 5: 389-393. PMID: 8054683, PMCID: PMC301049, DOI: 10.1091/mbc.5.4.389.Peer-Reviewed Original ResearchAlpha v integrins mediate the rise in intracellular calcium in endothelial cells on fibronectin even though they play a minor role in adhesion
Schwartz M, Denninghoff K. Alpha v integrins mediate the rise in intracellular calcium in endothelial cells on fibronectin even though they play a minor role in adhesion. Journal Of Biological Chemistry 1994, 269: 11133-11137. PMID: 7512559, DOI: 10.1016/s0021-9258(19)78101-0.Peer-Reviewed Original ResearchConceptsAlpha 5 beta 1Alpha vBeta 1Intracellular calciumEndothelial cellsAnti-integrin monoclonal antibodiesElevation of intracellularAlpha v integrinsAnti-integrin antibodiesMonoclonal antibodiesV integrinsAntibodiesDistinct intracellularAgonistsIntegrin alpha subunitsAdhesion assaysFunction-blocking anti-integrin antibodiesIntegrinsSpecific integrinsCalciumFibronectinAlpha subunitCellsSame cellsIntracellular