2023
Intracellular tension sensor reveals mechanical anisotropy of the actin cytoskeleton
Amiri S, Muresan C, Shang X, Huet-Calderwood C, Schwartz M, Calderwood D, Murrell M. Intracellular tension sensor reveals mechanical anisotropy of the actin cytoskeleton. Nature Communications 2023, 14: 8011. PMID: 38049429, PMCID: PMC10695988, DOI: 10.1038/s41467-023-43612-5.Peer-Reviewed Original ResearchConceptsF-actin architectureStress fibersCortical actinActin cytoskeletonMolecular tension sensorsF-actin stress fibersF-actin cytoskeletonFilamentous actin cytoskeletonMechanical forcesTension sensorCell divisionCytoskeletonCell migrationExtracellular matrixMyosin inhibitionActinDirection of stretchCellsCell axisUniaxial stretchStretchFRET
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
2015
Regulation of integrin-mediated adhesions
Iwamoto DV, Calderwood DA. Regulation of integrin-mediated adhesions. Current Opinion In Cell Biology 2015, 36: 41-47. PMID: 26189062, PMCID: PMC4639423, DOI: 10.1016/j.ceb.2015.06.009.Peer-Reviewed Original ResearchConceptsIntegrin-mediated adhesionHeterodimeric transmembrane adhesion receptorsShort cytoplasmic tailTransmembrane adhesion receptorsSpecific intracellular proteinsClustering of integrinsMetazoan developmentActin cytoskeletonExtracellular ligandsCytoplasmic tailIntracellular traffickingExtracellular environmentIntracellular proteinsAdhesion receptorsAdhesive structuresIntegrin receptorsCell membraneRelay signalsIntegrinsEssential roleMechanical forcesCell attachmentAdhesionRecent advancesCytoskeletonDirect Interactions with the Integrin β1 Cytoplasmic Tail Activate the Abl2/Arg Kinase*
Simpson MA, Bradley WD, Harburger D, Parsons M, Calderwood DA, Koleske AJ. Direct Interactions with the Integrin β1 Cytoplasmic Tail Activate the Abl2/Arg Kinase*. Journal Of Biological Chemistry 2015, 290: 8360-8372. PMID: 25694433, PMCID: PMC4375489, DOI: 10.1074/jbc.m115.638874.Peer-Reviewed Original ResearchConceptsIntegrin β1 cytoplasmic tailExtracellular matrix adhesion receptorsSrc homology domainFibroblast cell motilityIntegrin β1Β1 cytoplasmic tailMembrane-proximal segmentAdhesion complex formationMatrix adhesion receptorsNonreceptor tyrosine kinaseArg kinase activityArg nonreceptor tyrosine kinaseCancer cell invasivenessHomology domainActin cytoskeletonCytoplasmic tailCytoskeletal remodelingDendrite morphogenesisTyr-783Kinase domainPhosphorylated regionAbl familyΒ1 tailArg kinaseCell motility
2014
TRIM15 is a focal adhesion protein that regulates focal adhesion disassembly
Uchil PD, Pawliczek T, Reynolds TD, Ding S, Hinz A, Munro JB, Huang F, Floyd RW, Yang H, Hamilton WL, Bewersdorf J, Xiong Y, Calderwood DA, Mothes W. TRIM15 is a focal adhesion protein that regulates focal adhesion disassembly. Journal Of Cell Science 2014, 127: 3928-3942. PMID: 25015296, PMCID: PMC4163643, DOI: 10.1242/jcs.143537.Peer-Reviewed Original ResearchConceptsFocal adhesion proteinsFocal adhesionsCell migrationAdhesion proteinsMulti-adaptor proteinTripartite motif (TRIM) protein familyFocal adhesion dynamicsFocal adhesion turnoverFocal adhesion componentsCoiled-coil domainImpaired cell migrationII-independent mannerLD2 motifAdhesion turnoverActin cytoskeletonProtein familyAdhesion dynamicsCellular functionsDynamic turnoverMacromolecular complexesRegulatory componentsFocal contactsAdhesion componentsExtracellular matrixTRIM15
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 receptorsASB2α, 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 adhesionTalins 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
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 forcesMembraneFilamentsCytoskeletalMechanosensingCytoskeletonFilamin 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 mechanismDifferentiationTalin 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
Integrins in the Ovary
Monniaux D, Huet-Calderwood C, Bellego F, Fabre S, Monget P, Calderwood D. Integrins in the Ovary. Seminars In Reproductive Medicine 2006, 24: 251-261. PMID: 16944422, DOI: 10.1055/s-2006-948554.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRole of integrinsSperm ADAMsActin cytoskeletonExtracellular matrix componentsIntegrin tailsMultiple signalingOocyte integrinsOvarian surface epithelium cellsIntegrin functionConformational changesExtracellular matrixIntegrinsCell proliferationMatrix componentsTumor developmentMajor receptorIntegrin expressionSurface epithelium cellsPossible involvementPotential roleFollicular cellsGranulosa cellsCellsFollicular basement membraneEpithelium cellsThe 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
2003
Talin 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 Research
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
1999
The Talin Head Domain Binds to Integrin β Subunit Cytoplasmic Tails and Regulates Integrin Activation*
Calderwood D, Zent R, Grant R, Rees D, Hynes R, Ginsberg M. The Talin Head Domain Binds to Integrin β Subunit Cytoplasmic Tails and Regulates Integrin Activation*. Journal Of Biological Chemistry 1999, 274: 28071-28074. PMID: 10497155, DOI: 10.1074/jbc.274.40.28071.Peer-Reviewed Original ResearchConceptsTalin head domainIntegrin cytoplasmic tailsCytoplasmic tailIntegrin-binding siteHead domainActin cytoskeletonFragment of talinIntegrin beta tailsIntegrin adhesion receptorsSingle point mutationFocal adhesionsCytoplasmic domainCytoplasmic proteinsBeta tailsIntegrin functionIntegrin localizationTalinIntegrin activationIntegrin affinityActin filamentsAdhesion receptorsIntegrin-cytoskeletal interactionsPoint mutationsCytoskeletonStructural mimics