2017
Novel ecto-tagged integrins reveal their trafficking in live cells
Huet-Calderwood C, Rivera-Molina F, Iwamoto DV, Kromann EB, Toomre D, Calderwood DA. Novel ecto-tagged integrins reveal their trafficking in live cells. Nature Communications 2017, 8: 570. PMID: 28924207, PMCID: PMC5603536, DOI: 10.1038/s41467-017-00646-w.Peer-Reviewed Original ResearchConceptsIntegrin functionΒ1 integrinLive cellsCell surface adhesion receptorsHeterodimeric cell-surface adhesion receptorsIntegrin endocytosisMulticellular organismsNovel powerful toolFocal adhesionsKnockout fibroblastsIntegrin activationAdhesion receptorsExtracellular loopIntegrinsTraffickingMajor mysteriesCellsTagsAdhesionHaloTagEndocytosisPowerful toolExocytosisOrganismsVesicles
2016
Nuclear Localization of Integrin Cytoplasmic Domain-associated Protein-1 (ICAP1) Influences β1 Integrin Activation and Recruits Krev/Interaction Trapped-1 (KRIT1) to the Nucleus*
Draheim KM, Huet-Calderwood C, Simon B, Calderwood DA. Nuclear Localization of Integrin Cytoplasmic Domain-associated Protein-1 (ICAP1) Influences β1 Integrin Activation and Recruits Krev/Interaction Trapped-1 (KRIT1) to the Nucleus*. Journal Of Biological Chemistry 2016, 292: 1884-1898. PMID: 28003363, PMCID: PMC5290960, DOI: 10.1074/jbc.m116.762393.Peer-Reviewed Original Research
2014
Podocyte-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 talin1Differences in binding to the ILK complex determines kindlin isoform adhesion localization and integrin activation
Huet-Calderwood C, Brahme NN, Kumar N, Stiegler AL, Raghavan S, Boggon TJ, Calderwood DA. Differences in binding to the ILK complex determines kindlin isoform adhesion localization and integrin activation. Journal Of Cell Science 2014, 127: 4308-4321. PMID: 25086068, PMCID: PMC4179494, DOI: 10.1242/jcs.155879.Peer-Reviewed Original ResearchConceptsIntegrin activationKindlin-2Kindlin-3Focal adhesion proteinsFunctional differencesIntegrin-linked kinaseILK complexAdhesion proteinsF2 subdomainMolecular basisIsoform specificityComplex bindsKindlinFA targetingActivation defectsCell adhesionActivationFALocalizesKinaseGFPSignalingILKIsoformsProtein
2013
Kindlin Binds Migfilin Tandem LIM Domains and Regulates Migfilin Focal Adhesion Localization and Recruitment Dynamics*
Brahme NN, Harburger DS, Kemp-O'Brien K, Stewart R, Raghavan S, Parsons M, Calderwood DA. Kindlin Binds Migfilin Tandem LIM Domains and Regulates Migfilin Focal Adhesion Localization and Recruitment Dynamics*. Journal Of Biological Chemistry 2013, 288: 35604-35616. PMID: 24165133, PMCID: PMC3853305, DOI: 10.1074/jbc.m113.483016.Peer-Reviewed Original ResearchConceptsFocal adhesionsLIM domainsActin cytoskeletonFluorescence resonance energy transferFA localizationActin-rich stress fibersC-terminal LIM domainsLIM domain regionTandem LIM domainsTwo-hybrid screenDomain-containing adaptor proteinFocal adhesion localizationIntegrin-binding proteinsIntegrin adhesion receptorsPulldown assaysAdaptor proteinMigfilinFA formationKindlinRecruitment dynamicsStress fibersKindlin-2Integrin activationIntracellular proteinsAdhesion receptorsTalins 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 ResearchA 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
2009
Kindlin-1 and -2 Directly Bind the C-terminal Region of β Integrin Cytoplasmic Tails and Exert Integrin-specific Activation Effects*
Harburger DS, Bouaouina M, Calderwood DA. Kindlin-1 and -2 Directly Bind the C-terminal Region of β Integrin Cytoplasmic Tails and Exert Integrin-specific Activation Effects*. Journal Of Biological Chemistry 2009, 284: 11485-11497. PMID: 19240021, PMCID: PMC2670154, DOI: 10.1074/jbc.m809233200.Peer-Reviewed Original Research
2008
JAM-L–mediated leukocyte adhesion to endothelial cells is regulated in cis by α4β1 integrin activation
Luissint AC, Lutz PG, Calderwood DA, Couraud PO, Bourdoulous S. JAM-L–mediated leukocyte adhesion to endothelial cells is regulated in cis by α4β1 integrin activation. Journal Of Cell Biology 2008, 183: 1159-1173. PMID: 19064666, PMCID: PMC2600739, DOI: 10.1083/jcb.200805061.Peer-Reviewed Original ResearchConceptsJunctional adhesion moleculeIntegrin activationIntegrin-dependent adhesionIntegrin VLA-4Endothelial cellsAdhesion moleculesEpithelial adhesion moleculesJAM familyHeterophilic interactionsCis dimerizationDimerization stateVLA-4Monomeric formLeukocyte integrin VLA-4CellsActivationAdhesionComplexesProteinMoleculesDimerizationLeukocyte adhesionRecruitmentAccumulationFamily
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