2024
Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis
Chanduri M, Kumar A, Weiss D, Emuna N, Barsukov I, Shi M, Tanaka K, Wang X, Datye A, Kanyo J, Collin F, Lam T, Schwarz U, Bai S, Nottoli T, Goult B, Humphrey J, Schwartz M. Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis. Science Advances 2024, 10: eadi6286. PMID: 39167642, PMCID: PMC11338229, DOI: 10.1126/sciadv.adi6286.Peer-Reviewed Original ResearchConceptsTissue mechanical homeostasisStiffness sensingExtracellular matrixTalin-1Mechanical homeostasisExtracellular matrix mechanicsIncreased cell spreadingCell spreadingTalinMutationsCellular sensingFibrillar collagenReduced axial stiffnessTissue mechanical propertiesMechanical propertiesAxial stiffnessCompliant substratesHomeostasisRupture pressureArp2/3ARPC5LStiffnessHomeostasis hypothesisResident cellsTissue stiffness
2021
Epistatic interaction of PDE4DIP and DES mutations in familial atrial fibrillation with slow conduction
Ziki M, Bhat N, Neogi A, Driscoll TP, Ugwu N, Liu Y, Smith E, Abboud JM, Chouairi S, Schwartz MA, Akar JG, Mani A. Epistatic interaction of PDE4DIP and DES mutations in familial atrial fibrillation with slow conduction. Human Mutation 2021, 42: 1279-1293. PMID: 34289528, PMCID: PMC8434967, DOI: 10.1002/humu.24265.Peer-Reviewed Original ResearchConceptsEarly-onset atrial fibrillationAtrial fibrillationHeart blockFamilial atrial fibrillationSlow conductionDES mutationsSlow atrial fibrillationWhole-exome sequencingConduction diseaseIsoproterenol stimulationExome sequencingGenetic causePathogenic mutationsPDE4DIPReduced colocalizationHigh penetranceGenetic screeningUnrelated kindredsFibrillationPKA phosphorylationDesmin geneEpistatic interactionsT substitutionKindredsPDE4D
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 edgeABS2SitesInteraction
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
2017
Live imaging molecular changes in junctional tension upon VE-cadherin in zebrafish
Lagendijk AK, Gomez GA, Baek S, Hesselson D, Hughes WE, Paterson S, Conway DE, Belting HG, Affolter M, Smith KA, Schwartz MA, Yap AS, Hogan BM. Live imaging molecular changes in junctional tension upon VE-cadherin in zebrafish. Nature Communications 2017, 8: 1402. PMID: 29123087, PMCID: PMC5680264, DOI: 10.1038/s41467-017-01325-6.Peer-Reviewed Original ResearchConceptsVE-cadherinEndothelial cell-cell junctionsCell-cell junctionsActo-myosin cytoskeletonTension sensorActo-myosin contractilityJunctional tensionEmbryonic developmentDiverse rolesVascular developmentLive zebrafishChemical perturbationsFRET measurementsZebrafishAdjacent cellsMolecular changesEndothelial cellsCellsBiosensor approachCytoskeletonHomeostasisLocalizationVivoTensile changesMatures
2015
KLF4 is a key determinant in the development and progression of cerebral cavernous malformations
Cuttano R, Rudini N, Bravi L, Corada M, Giampietro C, Papa E, Morini MF, Maddaluno L, Baeyens N, Adams RH, Jain MK, Owens GK, Schwartz M, Lampugnani MG, Dejana E. KLF4 is a key determinant in the development and progression of cerebral cavernous malformations. EMBO Molecular Medicine 2015, 8: 6-24. PMID: 26612856, PMCID: PMC4718159, DOI: 10.15252/emmm.201505433.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Morphogenetic Protein 6Cell ProliferationDisease Models, AnimalDisease ProgressionEndothelial CellsHEK293 CellsHemangioma, Cavernous, Central Nervous SystemHumansKRIT1 ProteinKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceMice, Inbred C57BLMice, KnockoutMicrotubule-Associated ProteinsMitogen-Activated Protein Kinase 7MutationProto-Oncogene ProteinsRNA InterferenceSignal TransductionSmad1 ProteinTransforming Growth Factor betaConceptsKruppel-like factor 4Cerebral cavernous malformationsEndothelial cellsCavernous malformationsFamilial cerebral cavernous malformationsCentral nervous systemDouble knockout miceGrowth factor-beta/bone morphogenetic protein signalingCerebral hemorrhageMouse mortalityPharmacological treatmentCurrent therapiesVascular malformationsKnockout miceTherapeutic targetNervous systemMesenchymal transitionKLF4 transcriptional activityMalformationsCCM3 genesFactor 4Function mutationsEndMTMorphogenetic protein signalingBone morphogenetic protein (BMP) signaling
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
2006
Integrin-mediated adhesion regulates membrane order
Gaus K, Le Lay S, Balasubramanian N, Schwartz MA. Integrin-mediated adhesion regulates membrane order. Journal Of Cell Biology 2006, 174: 725-734. PMID: 16943184, PMCID: PMC2064315, DOI: 10.1083/jcb.200603034.Peer-Reviewed Original ResearchConceptsFocal adhesionsMembrane orderCholesterol-dependent domainsSpecific protein complexesLipid raft propertiesIntegrin-mediated adhesionFluorescent probe LaurdanProtein complexesRaft componentsDetachment of cellsRaft propertiesCell adhesionCell membraneSubunit BProbe LaurdanCaveolinCaveolaeAdhesionDomainImportant consequencesTyr14Caveolin1PhosphorylationTraffickingTwo-photon microscopy
2003
Modulation 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 roleLocalizationK44AGTPasesMacropinosomesInvadopodiaRho-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
A Dominant-Negative p65 PAK Peptide Inhibits Angiogenesis
Kiosses WB, Hood J, Yang S, Gerritsen ME, Cheresh DA, Alderson N, Schwartz MA. A Dominant-Negative p65 PAK Peptide Inhibits Angiogenesis. Circulation Research 2002, 90: 697-702. PMID: 11934838, DOI: 10.1161/01.res.0000014227.76102.5d.Peer-Reviewed Original ResearchIntegrins regulate the apoptotic response to DNA damage through modulation of p53
Lewis JM, Truong TN, Schwartz MA. Integrins regulate the apoptotic response to DNA damage through modulation of p53. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 3627-3632. PMID: 11904424, PMCID: PMC122574, DOI: 10.1073/pnas.062698499.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodiesApoptosisCaspase 3CaspasesCell AdhesionCell SurvivalChromosome AberrationsCyclin-Dependent Kinase Inhibitor p16DNA DamageFibroblastsHumansIntegrinsMelanomaMiceMutationNuclear ProteinsOrgan SpecificityProto-Oncogene ProteinsProto-Oncogene Proteins c-mdm2Radiation, IonizingSarcomaTumor Cells, CulturedTumor Suppressor Protein p14ARFTumor Suppressor Protein p53ConceptsTumor cellsTherapy-resistant tumorsModulation of p53Susceptible tumor cellsDNA damageLevels of p53Low p53 levelsApoptosis of cellsTherapy resistanceAntiintegrin antibodiesCancer cellsP53 levelsSurvival of cellsP53Nonadherent cellsCell typesSurvivalApoptotic responseCellsP19 ARFApoptosisChromosomal instabilityFibroblastic cell typesDamageChemotherapy
2000
Adhesion to the extracellular matrix regulates the coupling of the small GTPase Rac to its effector PAK
del Pozo M, Price L, Alderson N, Ren X, Schwartz M. Adhesion to the extracellular matrix regulates the coupling of the small GTPase Rac to its effector PAK. The EMBO Journal 2000, 19: 2008-2014. PMID: 10790367, PMCID: PMC305684, DOI: 10.1093/emboj/19.9.2008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological TransportCdc42 GTP-Binding ProteinCell AdhesionCell LineCell MembraneCulture Media, Serum-FreeCytoplasmEnzyme ActivationExtracellular MatrixFibronectinsGrowth SubstancesGuanosine TriphosphateIntegrinsMiceMutationMyristic AcidP21-Activated KinasesProtein BindingProtein Serine-Threonine KinasesRac GTP-Binding ProteinsRatsRecombinant Fusion ProteinsTransfectionConceptsSmall GTPase RacExtracellular matrixGTPase RacEffector PAKMembrane-targeting sequenceCell cycle progressionAbility of RacSoluble growth factorsAdherent cellsRac mutantGrowth factorCytoskeletal organizationPAK activationOncogenic transformationGene expressionCycle progressionMembrane fractionCell adhesionNon-adherent cellsRacPAKMembraneCellsAdhesionActivation
1993
Signaling by integrins: implications for tumorigenesis.
Schwartz M. Signaling by integrins: implications for tumorigenesis. Cancer Research 1993, 53: 1503-6. PMID: 8453614.Peer-Reviewed Original Research