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
2014
The Talin Head Domain Reinforces Integrin-Mediated Adhesion by Promoting Adhesion Complex Stability and Clustering
Ellis SJ, Lostchuck E, Goult BT, Bouaouina M, Fairchild MJ, López-Ceballos P, Calderwood DA, Tanentzapf G. The Talin Head Domain Reinforces Integrin-Mediated Adhesion by Promoting Adhesion Complex Stability and Clustering. PLOS Genetics 2014, 10: e1004756. PMID: 25393120, PMCID: PMC4230843, DOI: 10.1371/journal.pgen.1004756.Peer-Reviewed Original ResearchPodocyte-associated talin1 is critical for glomerular filtration barrier maintenance
Tian X, Kim JJ, Monkley SM, Gotoh N, Nandez R, Soda K, Inoue K, Balkin DM, Hassan H, Son SH, Lee Y, Moeckel G, Calderwood DA, Holzman LB, Critchley DR, Zent R, Reiser J, Ishibe S. Podocyte-associated talin1 is critical for glomerular filtration barrier maintenance. Journal Of Clinical Investigation 2014, 124: 1098-1113. PMID: 24531545, PMCID: PMC3934159, DOI: 10.1172/jci69778.Peer-Reviewed Original ResearchConceptsNephrotic syndromeFoot process effacementLoss of talin1Glomerular filtration barrierGlomerular injuryMurine modelProcess effacementKidney's glomerular filtration barrierFiltration barrierGlomerular basement membraneSevere proteinuriaKidney failurePharmacologic inhibitionSyndromeBarrier maintenanceCalpain activityIntegrin activationEpithelial cellsPodocytesModest reductionΒ1 integrin activationBasement membranePathogenesisInjuryCytoskeletal protein talin1
2013
Talins and kindlins: partners in integrin-mediated adhesion
Calderwood DA, Campbell ID, Critchley DR. Talins and kindlins: partners in integrin-mediated adhesion. Nature Reviews Molecular Cell Biology 2013, 14: 503-517. PMID: 23860236, PMCID: PMC4116690, DOI: 10.1038/nrm3624.Peer-Reviewed Original ResearchConceptsIntegrin activationAdhesion complexesTalin headAmino-terminal headTalin-vinculin interactionsIntegrin cytoplasmic domainIntegrin activation pathwaysIntegrin extracellular domainIntegrin subunitsShort cytoplasmic tailDefective integrin activationPost-translational modificationsFull-length talinTalin-integrin interactionActin-binding siteImportant control pointTransmit chemicalTalin autoinhibitionDisease-causing mutationsKey PointsIntegrinsActin cytoskeletonProtein talinExtracellular ligandsFocal adhesionsIntegrin tails
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 cultureCell Adhesion: A FERM Grasp of the Tail Sorts Out Integrins
Brahme NN, Calderwood DA. Cell Adhesion: A FERM Grasp of the Tail Sorts Out Integrins. Current Biology 2012, 22: r692-r694. PMID: 22974999, PMCID: PMC5507346, DOI: 10.1016/j.cub.2012.07.049.Peer-Reviewed Original ResearchFAK 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 sitesA Conserved Lipid-binding Loop in the Kindlin FERM F1 Domain Is Required for Kindlin-mediated αIIbβ3 Integrin Coactivation*
Bouaouina M, Goult BT, Huet-Calderwood C, Bate N, Brahme NN, Barsukov IL, Critchley DR, Calderwood DA. A Conserved Lipid-binding Loop in the Kindlin FERM F1 Domain Is Required for Kindlin-mediated αIIbβ3 Integrin Coactivation*. Journal Of Biological Chemistry 2012, 287: 6979-6990. PMID: 22235127, PMCID: PMC3293583, DOI: 10.1074/jbc.m111.330845.Peer-Reviewed Original ResearchConceptsIntegrin β tailsTalin FERM domainFERM domainFocal adhesionsΒ tailTalin headHeterodimeric integrin adhesion receptorsIntegrin activationKindlin-1Membrane-binding motifFERM domain proteinsIntegrin β subunitsShort cytoplasmic tailAcidic membrane phospholipidsIntegrin adhesion receptorsΑIIbβ3 integrin activationDomain proteinsIntegrin tailsCytoplasmic domainCytoplasmic tailKindlinKindlin familyDomain interactionsPhospholipid head groupsPolylysine motifNanopatterning reveals an ECM area threshold for focal adhesion assembly and force transmission that is regulated by integrin activation and cytoskeleton tension
Coyer SR, Singh A, Dumbauld DW, Calderwood DA, Craig SW, Delamarche E, García AJ. Nanopatterning reveals an ECM area threshold for focal adhesion assembly and force transmission that is regulated by integrin activation and cytoskeleton tension. Journal Of Cell Science 2012, 125: 5110-5123. PMID: 22899715, PMCID: PMC3533393, DOI: 10.1242/jcs.108035.Peer-Reviewed Original ResearchConceptsFocal adhesionsForce transductionFA assemblyCytoskeletal tensionExtracellular matrixIntegrin activationFocal adhesion assemblyVinculin head domainExpression of talinNon-migrating cellsVinculin mutantsCytoskeleton tensionAdhesion assemblyECM ligandsMyosin contractilityAdhesive areaStable assemblyIntracellular pathwaysTransductionAssemblyStructural linkPathwayStructural linkagesTraction forceCells
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
2010
Structure of a double ubiquitin‐like domain in the talin head: a role in integrin activation
Goult BT, Bouaouina M, Elliott PR, Bate N, Patel B, Gingras AR, Grossmann JG, Roberts GC, Calderwood DA, Critchley DR, Barsukov IL. Structure of a double ubiquitin‐like domain in the talin head: a role in integrin activation. The EMBO Journal 2010, 29: 1069-1080. PMID: 20150896, PMCID: PMC2845276, DOI: 10.1038/emboj.2010.4.Peer-Reviewed Original Research
2009
The Structure of the N-Terminus of Kindlin-1: A Domain Important for αIIbβ3 Integrin Activation
Goult BT, Bouaouina M, Harburger DS, Bate N, Patel B, Anthis NJ, Campbell ID, Calderwood DA, Barsukov IL, Roberts GC, Critchley DR. The Structure of the N-Terminus of Kindlin-1: A Domain Important for αIIbβ3 Integrin Activation. Journal Of Molecular Biology 2009, 394: 944-956. PMID: 19804783, PMCID: PMC2963925, DOI: 10.1016/j.jmb.2009.09.061.Peer-Reviewed Original Research
2008
Integrin signalling at a glance
Harburger DS, Calderwood DA. Integrin signalling at a glance. Journal Of Cell Science 2008, 122: 159-163. PMID: 19118207, PMCID: PMC2714413, DOI: 10.1242/jcs.018093.Peer-Reviewed Original Research
2007
The N-terminal Domains of Talin Cooperate with the Phosphotyrosine Binding-like Domain to Activate β1 and β3 Integrins*
Bouaouina M, Lad Y, Calderwood DA. The N-terminal Domains of Talin Cooperate with the Phosphotyrosine Binding-like Domain to Activate β1 and β3 Integrins*. Journal Of Biological Chemistry 2007, 283: 6118-6125. PMID: 18165225, DOI: 10.1074/jbc.m709527200.Peer-Reviewed Original Research
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 bindingActivationBindingTailAffinity