2024
DNA-Based Molecular Clamp for Probing Protein Interactions and Structure under Force
Chung M, Zhou K, Powell J, Lin C, Schwartz M. DNA-Based Molecular Clamp for Probing Protein Interactions and Structure under Force. ACS Nano 2024, 18: 27590-27596. PMID: 39344156, PMCID: PMC11518680, DOI: 10.1021/acsnano.4c08663.Peer-Reviewed Original ResearchConceptsTalin rod domainNegative-stain electron microscopyDouble-stranded DNADNA clampProtein functionRod domainCryptic sitesProtein interactionsMolecular clampCellular mechanotransductionStudy proteinsBiochemical studiesCell biologyAdult physiologyProtein conformationTalinProteinBiochemical scaleMultiple diseasesDNAARPC5LVinculinStructural analysisEmbryogenesisDNA-based devicesCross-regulations of two connected domains form a mechanical circuit for steady force transmission during clathrin-mediated endocytosis
Ren Y, Yang J, Fujita B, Zhang Y, Berro J. Cross-regulations of two connected domains form a mechanical circuit for steady force transmission during clathrin-mediated endocytosis. Cell Reports 2024, 43: 114725. PMID: 39276354, PMCID: PMC11476202, DOI: 10.1016/j.celrep.2024.114725.Peer-Reviewed Original ResearchClathrin-mediated endocytosisF-actinActin cytoskeletonFission yeast Schizosaccharomyces pombeYeast Schizosaccharomyces pombeCell adhesion complexAdhesion complexesMembrane localizationPN forcesStable bindingEnd4pCross-regulationCytoskeletonActinEndocytosisMembraneBindingMechanical forcesTalinTransmission of forcesThatchForce transmissionDomainCellsFissionCellular 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
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
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
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 transmissionCytoskeletonStrainsStretchAdhesionReexpression
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 evidenceDomainLocal Tension on Talin in Focal Adhesions Correlates with F-Actin Alignment at the Nanometer Scale
Kumar A, Anderson KL, Swift MF, Hanein D, Volkmann N, Schwartz MA. Local Tension on Talin in Focal Adhesions Correlates with F-Actin Alignment at the Nanometer Scale. Biophysical Journal 2018, 115: 1569-1579. PMID: 30274833, PMCID: PMC6372196, DOI: 10.1016/j.bpj.2018.08.045.Peer-Reviewed Original ResearchConceptsActin organizationLocal actin organizationTalin tension sensorFocal adhesion dynamicsLinear actin filamentsIndividual focal adhesionsCellular force transmissionF-actin alignmentFocal adhesionsAdhesion dynamicsCell centerVinculin localizationActin intensityActin filamentsF-actinAdhesion centersNormal physiologyTalinSame cellsAdhesion correlatesStable adhesionTension sensor
2016
Talin tension sensor reveals novel features of focal adhesion force transmission and mechanosensitivity
Kumar A, Ouyang M, Van den Dries K, McGhee EJ, Tanaka K, Anderson MD, Groisman A, Goult BT, Anderson KI, Schwartz MA. Talin tension sensor reveals novel features of focal adhesion force transmission and mechanosensitivity. Journal Of Cell Biology 2016, 213: 371-383. PMID: 27161398, PMCID: PMC4862330, DOI: 10.1083/jcb.201510012.Peer-Reviewed Original ResearchConceptsTalin tension sensorFar C-terminusIntegrin-dependent adhesionPeripheral adhesionsTension sensorFocal adhesionsCellular mechanosensingMechanosensitive structuresTalin functionC-terminusDistinct functionsRod domainStiffness sensingTalinVinculinActin filamentsABS3Site 2Soft substratesAdhesionForce transmissionMechanosensingNew lightTerminus
2012
Zasp regulates integrin activation
Bouaouina M, Jani K, Long JY, Czerniecki S, Morse EM, Ellis SJ, Tanentzapf G, Schöck F, Calderwood DA. Zasp regulates integrin activation. Journal Of Cell Science 2012, 125: 5647-5657. PMID: 22992465, PMCID: PMC3575701, DOI: 10.1242/jcs.103291.Peer-Reviewed Original ResearchConceptsIntegrin activationDomain-containing proteinsExtracellular matrixHeterodimeric adhesion receptorsPDZ motif-containing proteinΑ5β1 integrinMammalian tissue cultureScaffold proteinCytoplasmic tailFirst proteinECM ligandsMuscle contractile machineryΒ-integrinExtracellular domainAdhesion receptorsIntegrin heterodimersTalinConformational changesHigh-affinity bindingEssential processProteinIntegrinsHuman cardiomyopathyZASPTissue cultureFAK promotes recruitment of talin to nascent adhesions to control cell motility
Lawson C, Lim ST, Uryu S, Chen XL, Calderwood DA, Schlaepfer DD. FAK promotes recruitment of talin to nascent adhesions to control cell motility. Journal Of Cell Biology 2012, 196: 223-232. PMID: 22270917, PMCID: PMC3265949, DOI: 10.1083/jcb.201108078.Peer-Reviewed Original ResearchConceptsFocal adhesion kinaseNascent adhesionsCell motilityCell migrationRecruitment of talinCytoskeletal protein talinTension-independent mannerCytoskeletal-associated proteinDirect binding siteTalin associationProtein talinFAK recruitmentAdhesion dynamicsAdhesion kinaseFAK localizationTalinAdhesion sitesTalin cleavageIntegrin receptorsΒ1 integrinPoint mutationsNew adhesionsBinding sites
2011
Talin and Signaling Through Integrins
Bouaouina M, Harburger DS, Calderwood DA. Talin and Signaling Through Integrins. Methods In Molecular Biology 2011, 757: 325-347. PMID: 21909921, PMCID: PMC5642996, DOI: 10.1007/978-1-61779-166-6_20.Peer-Reviewed Original ResearchConceptsCytoplasmic tailIntegrin activationIntegrin β tailsAbility of integrinsIntegrin cytoplasmic tailsShort cytoplasmic tailIntegrin adhesion receptorsBinding of talinDominant-negative constructMulticellular animalsActin cytoskeletonΒ tailExtracellular ligandsTalin domainTalinCharacterization of interactionsIntracellular signalsAdhesion receptorsCell adhesionIntegrin receptorsCultured cellsExtracellular matrixNegative constructsIntegrin subunitsIntegrins
2006
Reconstructing and Deconstructing Agonist-Induced Activation of Integrin αIIbβ3
Han J, Lim CJ, Watanabe N, Soriani A, Ratnikov B, Calderwood DA, Puzon-McLaughlin W, Lafuente EM, Boussiotis VA, Shattil SJ, Ginsberg MH. Reconstructing and Deconstructing Agonist-Induced Activation of Integrin αIIbβ3. Current Biology 2006, 16: 1796-1806. PMID: 16979556, DOI: 10.1016/j.cub.2006.08.035.Peer-Reviewed Original ResearchConceptsIntegrin activationIntegrin affinityIntegrin beta cytoplasmic domainsIntegrin-associated complexesAgonist stimulationBeta cytoplasmic domainsIntegrin activation pathwaysProtein kinase CalphaExtracellular matrix assemblyBinding of talinSiRNA-mediated knockdownTumor cell metastasisRap effectorMulticellular animalsPhorbol myristate acetateSynthetic geneticsCytoplasmic domainRap1 GTPaseTransmembrane alphaActivation complexCytoskeletal proteinsTalinBeta subunitIntegrin αIIbβ3Cell adhesionThe Molecular Basis of Filamin Binding to Integrins and Competition with Talin
Kiema T, Lad Y, Jiang P, Oxley CL, Baldassarre M, Wegener KL, Campbell ID, Ylänne J, Calderwood DA. The Molecular Basis of Filamin Binding to Integrins and Competition with Talin. Molecular Cell 2006, 21: 337-347. PMID: 16455489, DOI: 10.1016/j.molcel.2006.01.011.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesCalpainContractile ProteinsCrystallography, X-RayFilaminsIntegrin beta ChainsMiceMicrofilament ProteinsModels, MolecularMolecular Sequence DataNIH 3T3 CellsNuclear Magnetic Resonance, BiomolecularProtein BindingProtein ConformationProtein Structure, TertiaryRecombinant Fusion ProteinsReproducibility of ResultsSequence Homology, Amino AcidTalinConceptsAdhesion receptorsTalin-dependent integrin activationActin-crosslinking proteinsIntegrin adhesion receptorsHigh-resolution structuresFilamin bindingExtended beta strandActin cytoskeletonIntegrin tailsMultiple transmembraneMolecular basisStrands CBeta strandsDomain interactionsBiochemical signalsIntegrin functionIntegrin activationFilamin ATalinCell membraneTail formsCytoskeletonProteinBinding sitesFilamin
2004
Talin controls integrin activation
Calderwood DA. Talin controls integrin activation. Biochemical Society Transactions 2004, 32: 434-437. PMID: 15157154, DOI: 10.1042/bst0320434.Peer-Reviewed Original ResearchConceptsIntegrin beta tailsIntegrin activationCytoplasmic domainBeta tailsMajor actin-binding proteinIntegrin beta cytoplasmic domainsBeta cytoplasmic domainsIntegrin cytoplasmic domainIntegrin activation pathwaysCytoskeletal protein talinIntegrin extracellular domainActin-binding proteinsIntegrin adhesion receptorsBinding of talinTalin FERM domainIntegrin-binding siteMulticellular organismsPTB domainFERM domainProtein talinExtracellular ligandsTalin expressionRNA interferenceTalinIntracellular signalsCompetition for Talin Results in Trans-dominant Inhibition of Integrin Activation*
Calderwood DA, Tai V, Di Paolo G, De Camilli P, Ginsberg MH. Competition for Talin Results in Trans-dominant Inhibition of Integrin Activation*. Journal Of Biological Chemistry 2004, 279: 28889-28895. PMID: 15143061, DOI: 10.1074/jbc.m402161200.Peer-Reviewed Original ResearchConceptsTrans-dominant inhibitionIntegrin activationFragment of talinCytoskeletal protein talinIntegrin adhesion receptorsMulticellular animalsProtein talinExtracellular ligandsCellular processesBeta tailsTalinTransdominant inhibitionAdhesion receptorsDifferent integrinsOverexpression of integrinsIntegrinsActivationClot retractionInhibitionReceptorsTailAdhesionSpeciesProteinOverexpressionIntegrin activation
Calderwood DA. Integrin activation. Journal Of Cell Science 2004, 117: 657-666. PMID: 14754902, DOI: 10.1242/jcs.01014.Peer-Reviewed Original ResearchConceptsIntegrin cytoplasmic domainExtracellular matrixCell-ECM adhesionIntegrin extracellular domainCytoskeletal protein talinTransmembrane adhesion receptorsAbility of cellsMulticellular organismsProtein talinExtracellular ligandsCytoplasmic domainIntegrin activationIntracellular signalsExtracellular domainAdhesion receptorsIntegrin familyConformational changesIntegrin receptorsIntracellular stepsReversible mechanismRecent studiesAdhesionTalinReceptorsOrganisms
2003
Talin Binding to Integrin ß Tails: A Final Common Step in Integrin Activation
Tadokoro S, Shattil SJ, Eto K, Tai V, Liddington RC, de Pereda J, Ginsberg MH, Calderwood DA. Talin Binding to Integrin ß Tails: A Final Common Step in Integrin Activation. Science 2003, 302: 103-106. PMID: 14526080, DOI: 10.1126/science.1086652.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acid SubstitutionAnimalsAntibodies, MonoclonalCell LineFibronectinsHumansIntegrin beta ChainsIntegrin beta1Integrin beta3Molecular Sequence DataMutationPlatelet Glycoprotein GPIIb-IIIa ComplexProtein BindingProtein ConformationProtein Structure, TertiaryRecombinant ProteinsRNA, Small InterferingSignal TransductionTalinTransfectionConceptsIntegrin activationCytoplasmic tailIntegrin betaCytoskeletal protein talinIntegrin extracellular domainCellular signaling cascadesIntegrin beta tailsNormal cell adhesionBinding of talinProtein talinBeta tailsSignaling cascadesIntegrin affinityConformational rearrangementsExtracellular domainFinal common stepTalinCell adhesionExtracellular matrixCommon stepSpecific bindingActivationBindingTailAffinityTalin forges the links between integrins and actin
Calderwood DA, Ginsberg MH. Talin forges the links between integrins and actin. Nature Cell Biology 2003, 5: 694-696. PMID: 12894175, DOI: 10.1038/ncb0803-694.Peer-Reviewed Original ResearchStructural Determinants of Integrin Recognition by Talin
Garcı́a-Alvarez B, de Pereda JM, Calderwood DA, Ulmer TS, Critchley D, Campbell ID, Ginsberg MH, Liddington RC. Structural Determinants of Integrin Recognition by Talin. Molecular Cell 2003, 11: 49-58. PMID: 12535520, DOI: 10.1016/s1097-2765(02)00823-7.Peer-Reviewed Original ResearchConceptsBidirectional signal transductionFragment of talinIntegrin adhesion receptorsFERM domainIntegrin tailsCytoplasmic domainCytoplasmic proteinsSignal transductionIntegrin linkagesTransmembrane receptorsTalinMutational analysisAdhesion receptorsDomain recognitionCell interiorIntegrin recognitionStructural determinantsLigand interactionsNovel variantsStructural paradigmFragmentsTransductionReceptorsTailDomain
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