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
Structural basis of the filamin A actin-binding domain interaction with F-actin
Iwamoto DV, Huehn A, Simon B, Huet-Calderwood C, Baldassarre M, Sindelar CV, Calderwood DA. Structural basis of the filamin A actin-binding domain interaction with F-actin. Nature Structural & Molecular Biology 2018, 25: 918-927. PMID: 30224736, PMCID: PMC6173970, DOI: 10.1038/s41594-018-0128-3.Peer-Reviewed Original ResearchConceptsActin-binding domainCalponin homology domainHomology domainF-actinActin cross-linking proteinFunction mutationsTandem calponin homology domainsDisease-associated mutantsCryo-electron microscopyHigh-resolution structuresNumerous genetic diseasesSequence conservationHigher-order structureLinking proteinStructural basisDomain interactionsCell shapeActin filamentsMolecular understandingN-terminalFunctional studiesGenetic diseasesMissense mutationsMutationsAtomic resolution
2013
ASB2α, an E3 Ubiquitin Ligase Specificity Subunit, Regulates Cell Spreading and Triggers Proteasomal Degradation of Filamins by Targeting the Filamin Calponin Homology 1 Domain*
Razinia Z, Baldassarre M, Cantelli G, Calderwood DA. ASB2α, an E3 Ubiquitin Ligase Specificity Subunit, Regulates Cell Spreading and Triggers Proteasomal Degradation of Filamins by Targeting the Filamin Calponin Homology 1 Domain*. Journal Of Biological Chemistry 2013, 288: 32093-32105. PMID: 24052262, PMCID: PMC3814802, DOI: 10.1074/jbc.m113.496604.Peer-Reviewed Original ResearchConceptsHematopoietic cell differentiationSpecificity subunitProteasomal degradationF-actin-rich structuresE3 ubiquitin ligase complexCell differentiationNormal subcellular localizationHomology 1 domainLoss of filaminUbiquitin acceptor sitesActin-binding domainCross-linking proteinsActin-binding siteLigase complexActin cytoskeletonTransmembrane proteinSubcellular localizationΑ-actinin1Transient expressionASB2αDegradation of filaminMinimal fragmentLysine residuesFilaminCell adhesion
2012
Filamins in Mechanosensing and Signaling
Razinia Z, Mäkelä T, Ylänne J, Calderwood DA. Filamins in Mechanosensing and Signaling. Annual Review Of Biophysics 2012, 41: 227-246. PMID: 22404683, PMCID: PMC5508560, DOI: 10.1146/annurev-biophys-050511-102252.Peer-Reviewed Original ResearchConceptsPlasma membraneActin filamentsActin-binding proteinsExtracellular matrix connectionsCortical rigidityActin cytoskeletonCellular functionsCell cortexTranscription factorsTransmembrane receptorsAdhesion proteinsCell shapeFilaminIon channelsDiverse arrayFunctional evidenceEssential roleProteinMatrix connectionsPhysical forcesMembraneFilamentsCytoskeletalMechanosensingCytoskeletonMacrophage Mesenchymal Migration Requires Podosome Stabilization by Filamin A*
Guiet R, Vérollet C, Lamsoul I, Cougoule C, Poincloux R, Labrousse A, Calderwood DA, Glogauer M, Lutz PG, Maridonneau-Parini I. Macrophage Mesenchymal Migration Requires Podosome Stabilization by Filamin A*. Journal Of Biological Chemistry 2012, 287: 13051-13062. PMID: 22334688, PMCID: PMC3339984, DOI: 10.1074/jbc.m111.307124.Peer-Reviewed Original ResearchConceptsFilamin AMesenchymal migrationEmbryonic developmentPodosome rosette formationCell migrationMesenchymal migration modeCertain cell typesPodosome stabilityScaffold proteinActin polymerizationAmoeboid migrationNull mutationPodosomesActin filamentsMigratory cellsAmoeboid modeCell typesOrgan defectsMigration modesNew functionsThree-dimensional environmentMutationsProteaseStrong consequencesFLNA mutationsFilamin A controls matrix metalloproteinase activity and regulates cell invasion in human fibrosarcoma cells
Baldassarre M, Razinia Z, Brahme NN, Buccione R, Calderwood DA. Filamin A controls matrix metalloproteinase activity and regulates cell invasion in human fibrosarcoma cells. Journal Of Cell Science 2012, 125: 3858-3869. PMID: 22595522, PMCID: PMC3462082, DOI: 10.1242/jcs.104018.Peer-Reviewed Original ResearchMeSH KeywordsActinsCell AdhesionCell Line, TumorCell MovementContractile ProteinsEnzyme ActivationExtracellular MatrixFibrosarcomaFilaminsGene Knockdown TechniquesHumansIntegrinsMatrix Metalloproteinase 14Matrix Metalloproteinase 2Microfilament ProteinsNeoplasm InvasivenessPhenotypeProtein Structure, TertiaryConceptsFilamin AActin cytoskeletonCell invasionActin-binding domainCell surface adhesion proteinsControls cell motilityActin-binding proteinsIntegrin adhesion receptorsRandom cell migrationAbility of cellsArray of intracellularBreast cancer lossSurface adhesion proteinsHuman fibrosarcoma cellsExtracellular matrix degradationMatrix metalloproteinase activityFilamin expressionKnockdown cellsAdhesion proteinsCell motilityMetalloproteinase activityActin filamentsAdhesion receptorsFilaminECM remodeling
2011
The E3 ubiquitin ligase specificity subunit ASB2α targets filamins for proteasomal degradation by interacting with the filamin actin-binding domain
Razinia Z, Baldassarre M, Bouaouina M, Lamsoul I, Lutz PG, Calderwood DA. The E3 ubiquitin ligase specificity subunit ASB2α targets filamins for proteasomal degradation by interacting with the filamin actin-binding domain. Journal Of Cell Science 2011, 124: 2631-2641. PMID: 21750192, PMCID: PMC3138704, DOI: 10.1242/jcs.084343.Peer-Reviewed Original ResearchConceptsFilamin degradationProteasomal degradationCell differentiationDomain of filaminActin-rich structuresUbiquitin-proteasome pathwayExtracellular matrix connectionsActin cytoskeletonTransmembrane proteinSubcellular localizationMolecular basisSignaling cascadesASB2αActin filamentsFilaminAcute degradationBiochemical assaysMyeloid leukemia cellsImportant familyActinEarly eventsProteinLeukemia cellsImportant mechanismDifferentiation
2009
Filamins Regulate Cell Spreading and Initiation of Cell Migration
Baldassarre M, Razinia Z, Burande CF, Lamsoul I, Lutz PG, Calderwood DA. Filamins Regulate Cell Spreading and Initiation of Cell Migration. PLOS ONE 2009, 4: e7830. PMID: 19915675, PMCID: PMC2773003, DOI: 10.1371/journal.pone.0007830.Peer-Reviewed Original ResearchConceptsCell spreadingLarge actin-binding proteinCell biological analysesCell migrationActin-binding proteinsLoss of FlnAShRNA-mediated knockdownInitiation of migrationInhibition of initiationRecent knockout studiesProteasomal degradationKnockdown cellsInitiation of motilityKnockout studiesFilaminSingle knockoutImpairs migrationFLNAFLNBBiological analysisKnockdownProteinObserved defectsCellsPeriventricular heterotopiaFilamin A–β1 Integrin Complex Tunes Epithelial Cell Response to Matrix Tension
Gehler S, Baldassarre M, Lad Y, Leight JL, Wozniak MA, Riching KM, Eliceiri KW, Weaver VM, Calderwood DA, Keely PJ. Filamin A–β1 Integrin Complex Tunes Epithelial Cell Response to Matrix Tension. Molecular Biology Of The Cell 2009, 20: 3224-3238. PMID: 19458194, PMCID: PMC2710838, DOI: 10.1091/mbc.e08-12-1186.Peer-Reviewed Original ResearchConceptsFilamin AExtracellular matrixProtein filamin AHigh-density gelsMatrix tensionCollagen gelsMechanosensitive complexBreast epithelial cellsCellular contractilityMatrix stiffnessMorphogenesisEpithelial cell responsesCell typesDuctal morphogenesisEpithelial cellsCellsCollagen matrixGel contractionActinCollagen remodelingIntegrinsCell responsesCollagen fibrilsRemodelingGelThe E3 ubiquitin ligase specificity subunit ASB2β is a novel regulator of muscle differentiation that targets filamin B to proteasomal degradation
Bello NF, Lamsoul I, Heuzé ML, Métais A, Moreaux G, Calderwood DA, Duprez D, Moog-Lutz C, Lutz PG. The E3 ubiquitin ligase specificity subunit ASB2β is a novel regulator of muscle differentiation that targets filamin B to proteasomal degradation. Cell Death & Differentiation 2009, 16: 921-932. PMID: 19300455, PMCID: PMC2709956, DOI: 10.1038/cdd.2009.27.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCarrier ProteinsCell DifferentiationCell LineChickensContractile ProteinsFilaminsGene Knockdown TechniquesHumansMiceMicrofilament ProteinsMyoblastsProteasome Endopeptidase ComplexRNA InterferenceRNA, MessengerSuppressor of Cytokine Signaling ProteinsUbiquitin-Protein LigasesConceptsFilamin BMuscle differentiationSpecificity subunitAnkyrin repeat-containing proteinActive E3 ubiquitin ligaseE3 ubiquitin ligase complexRepeat-containing proteinUbiquitin ligase complexE3 ubiquitin ligaseSuppressor of cytokineBox 2 geneLigase complexE3 ubiquitinUbiquitin ligaseProteasomal degradationMyoblast fusionNovel regulatorMuscle developmentKnockdown cellsProtein degradationMyogenic differentiationAdult tissuesC2C12 cellsMuscle contractile proteinsInduced differentiationThe Role of FilGAP-Filamin A Interactions in Mechanoprotection
Shifrin Y, Arora PD, Ohta Y, Calderwood DA, McCulloch CA. The Role of FilGAP-Filamin A Interactions in Mechanoprotection. Molecular Biology Of The Cell 2009, 20: 1269-1279. PMID: 19144823, PMCID: PMC2649276, DOI: 10.1091/mbc.e08-08-0872.Peer-Reviewed Original Research
2008
Structural Basis of the Migfilin-Filamin Interaction and Competition with Integrin β Tails*
Lad Y, Jiang P, Ruskamo S, Harburger DS, Ylänne J, Campbell ID, Calderwood DA. Structural Basis of the Migfilin-Filamin Interaction and Competition with Integrin β Tails*. Journal Of Biological Chemistry 2008, 283: 35154-35163. PMID: 18829455, PMCID: PMC2596399, DOI: 10.1074/jbc.m802592200.Peer-Reviewed Original ResearchConceptsCell-extracellular matrix adhesion sitesHuman filaminN-terminal actin-binding domainProtein-protein interaction studiesActin cross-linking protein filaminIntegrin β tailsMatrix adhesion sitesActin-binding domainIntegrin beta tailsN-terminal portionIntegrin-cytoskeleton linkagesImmunoglobulin-like domainsIntegrin tailsΒ tailAdaptor proteinMigfilinBeta tailsProtein filaminCommon binding siteMolecular basisStructural basisAdhesion sitesCell shapeFilaminCell adhesionASB2 targets filamins A and B to proteasomal degradation
Heuzé ML, Lamsoul I, Baldassarre M, Lad Y, Lévêque S, Razinia Z, Moog-Lutz C, Calderwood DA, Lutz PG. ASB2 targets filamins A and B to proteasomal degradation. Blood 2008, 112: 5130-5140. PMID: 18799729, PMCID: PMC2597609, DOI: 10.1182/blood-2007-12-128744.Peer-Reviewed Original ResearchConceptsAnkyrin repeat-containing proteinFilamin AE3 ubiquitin ligase complexActin-binding protein filamin AFilamin degradationRepeat-containing proteinUbiquitin ligase complexSeries of proliferationHematopoietic cell differentiationProtein filamin AAcid-induced differentiationSuppressor of cytokineLigase complexSpecificity subunitLeukemia cellsHematopoietic differentiationHematopoietic progenitor cellsProteasomal degradationMolecular basisAcute promyelocytic leukemia cellsSpecific proteinsCell spreadingPromyelocytic leukemia cellsArrest of differentiationCell differentiation
2007
Structure of three tandem filamin domains reveals auto‐inhibition of ligand binding
Lad Y, Kiema T, Jiang P, Pentikäinen OT, Coles CH, Campbell ID, Calderwood DA, Ylänne J. Structure of three tandem filamin domains reveals auto‐inhibition of ligand binding. The EMBO Journal 2007, 26: 3993-4004. PMID: 17690686, PMCID: PMC1948075, DOI: 10.1038/sj.emboj.7601827.Peer-Reviewed Original Research
2006
The 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
2001
Increased filamin binding to β-integrin cytoplasmic domains inhibits cell migration
Calderwood D, Huttenlocher A, Kiosses W, Rose D, Woodside D, Schwartz M, Ginsberg M. Increased filamin binding to β-integrin cytoplasmic domains inhibits cell migration. Nature Cell Biology 2001, 3: 1060-1068. PMID: 11781567, DOI: 10.1038/ncb1201-1060.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsBinding SitesCell MovementCell PolarityCHO CellsContractile ProteinsCricetinaeCytoplasmCytoskeletonFibronectinsFilaminsFocal AdhesionsHumansIntegrin beta ChainsIntegrinsIsoleucineJurkat CellsMicrofilament ProteinsProtein Structure, TertiaryRecombinant Fusion ProteinsTalinValineConceptsFocal adhesion formationFilamin bindingCell migrationMembrane protrusionsMatrix assemblyIntegrin-dependent cell migrationFibronectin matrix assemblyAmino acid substitutionsInhibits cell migrationAnimal developmentActin cytoskeletonIntegrin tailsBiochemical signalsAdhesion receptorsFilaminCell polarizationTalinAcid substitutionsExtracellular matrixAdhesion formationTailBindingAssemblyMigrationSelective loss
2000
Class- and Splice Variant-specific Association of CD98 with Integrin β Cytoplasmic Domains*
Zent R, Fenczik C, Calderwood D, Liu S, Dellos M, Ginsberg M. Class- and Splice Variant-specific Association of CD98 with Integrin β Cytoplasmic Domains*. Journal Of Biological Chemistry 2000, 275: 5059-5064. PMID: 10671548, DOI: 10.1074/jbc.275.7.5059.Peer-Reviewed Original ResearchConceptsCytoplasmic domainIntegrin activationMuscle-specific splice variantIntegrin beta cytoplasmic domainsBasic amino acid transportType II transmembrane proteinIntegrin β cytoplasmic domainBeta cytoplasmic domainsIntegrin cytoplasmic domainCell fusion eventsIntegrin adhesion receptorsAmino acid transportTransmembrane proteinMembrane proteinsFusion eventsIntegrin classAdhesion receptorsSplice variantsAcid transportCD98Variant specificityProteinIntegrinsDomainActivation