2023
Use of Ecto-Tagged Integrins to Monitor Integrin Exocytosis and Endocytosis
Huet-Calderwood C, Rivera-Molina F, Toomre D, Calderwood D. Use of Ecto-Tagged Integrins to Monitor Integrin Exocytosis and Endocytosis. Methods In Molecular Biology 2023, 2608: 17-38. PMID: 36653699, PMCID: PMC9999384, DOI: 10.1007/978-1-0716-2887-4_2.ChaptersConceptsΒ1 integrinTotal internal reflection fluorescence microscopyNormal cell adhesionIntegrin adhesion receptorsReflection fluorescence microscopyAdhesion receptorsCell adhesionEndocytosisFluorescence microscopyExocytosisIntegrinsCellsHaloTagPHluorinIntracellular labelingEctoPhotobleachingTagsReceptorsChaseFluorescentAdhesionLabelingMigration
2022
Fibroblasts secrete fibronectin under lamellipodia in a microtubule- and myosin II–dependent fashion
Huet-Calderwood C, Rivera-Molina F, Toomre D, Calderwood D. Fibroblasts secrete fibronectin under lamellipodia in a microtubule- and myosin II–dependent fashion. Journal Of Cell Biology 2022, 222: e202204100. PMID: 36416725, PMCID: PMC9699186, DOI: 10.1083/jcb.202204100.Peer-Reviewed Original ResearchConceptsFN secretionFocal adhesion dynamicsExtracellular matrixFocal adhesion formationSites of exocytosisLive-cell microscopyIntegrin-independent mannerCytoskeletal dynamicsFocal adhesionsAdhesion dynamicsRegulatory componentsMyosin IIIntact microtubulesCell polarizationCell adhesionIntegrin receptorsFN depositionLamellipodiaMicrotubulesFibronectinAdhesion formationNew adhesion formationFibroblastsII-dependent fashionCellsMolecular basis for integrin adhesion receptor binding to p21-activated kinase 4 (PAK4)
Ha B, Yigit S, Natarajan N, Morse E, Calderwood D, Boggon T. Molecular basis for integrin adhesion receptor binding to p21-activated kinase 4 (PAK4). Communications Biology 2022, 5: 1257. PMID: 36385162, PMCID: PMC9669019, DOI: 10.1038/s42003-022-04157-3.Peer-Reviewed Original ResearchConceptsP21-activated kinase 4Integrin adhesion receptorsMolecular basisAdhesion receptorsIntegrin β5Potential cellular rolesIntegrin β tailsKinase 4Membrane-proximal halfSubstrate-binding grooveSubstrate-binding siteSite-directed mutagenesisCellular rolesPhosphoacceptor sitesΒ tailExtracellular ligandsCytoplasmic signalingCytoplasmic tailKinase domainMultiple kinasesIntegrin complexΒ5 integrinsΒ5TailMutagenesisOrganization, dynamics and mechanoregulation of integrin-mediated cell–ECM adhesions
Kanchanawong P, Calderwood DA. Organization, dynamics and mechanoregulation of integrin-mediated cell–ECM adhesions. Nature Reviews Molecular Cell Biology 2022, 24: 142-161. PMID: 36168065, PMCID: PMC9892292, DOI: 10.1038/s41580-022-00531-5.Peer-Reviewed Original ResearchConceptsExtracellular matrixCell-ECM adhesionCell-ECM interactionsLocal extracellular matrixAdhesion maturationAdhesion complexesAnimal cellsBiochemical signalingTransmembrane receptorsAdhesion structuresCell shapeIntegrin familyMolecular natureAge-related dysfunctionAdvanced imaging approachesCharacterization of rearrangementsMechanical forcesSignalingTissue formationAdhesionCytoskeletonMechanoregulationImmune responseImaging approachImproved understanding
2020
Differences in self-association between kindlin-2 and kindlin-3 are associated with differential integrin binding
Kadry YA, Maisuria EM, Huet-Calderwood C, Calderwood DA. Differences in self-association between kindlin-2 and kindlin-3 are associated with differential integrin binding. Journal Of Biological Chemistry 2020, 295: 11161-11173. PMID: 32546480, PMCID: PMC7415974, DOI: 10.1074/jbc.ra120.013618.Peer-Reviewed Original ResearchConceptsKindlin-3Kindlin-2Focal adhesionsIntegrin cytoplasmic domainTransmembrane adhesion receptorsComparative sequence analysisLive-cell imagingAbility of cellsCytoplasmic domainF3 subdomainsMammalian cellsCytoplasmic componentsExtracellular environmentAdhesion receptorsKindlinSequence analysisIntegrin familySelf-associationIntegrin bindingPhysiological importanceMolecular levelPoint mutationsProteinCellsAdhesionChapter 22: Structural and signaling functions of integrins
Kadry YA, Calderwood DA. Chapter 22: Structural and signaling functions of integrins. Biochimica Et Biophysica Acta (BBA) - Biomembranes 2020, 1862: 183206. PMID: 31991120, PMCID: PMC7063833, DOI: 10.1016/j.bbamem.2020.183206.Peer-Reviewed Original ResearchConceptsFunction of integrinsAbility of integrinsTransmembrane adhesion receptorsNon-redundant functionsDifferent integrin heterodimersExtracellular matrix proteinsComplex structural rearrangementsDiverse downstreamCytoskeletal complexMetazoan lifeExtracellular environmentΒ-subunitAdhesion receptorsIntegrin heterodimersIntegrin familyMatrix proteinsCell adhesionIntegrinsStructural rearrangementsHeterodimersRecent advancesSubunitsSignalingProteinFunction
2019
Coarse-Grained Simulation of Full-Length Integrin Activation
Bidone TC, Polley A, Jin J, Driscoll T, Iwamoto DV, Calderwood DA, Schwartz MA, Voth GA. Coarse-Grained Simulation of Full-Length Integrin Activation. Biophysical Journal 2019, 116: 1000-1010. PMID: 30851876, PMCID: PMC6428961, DOI: 10.1016/j.bpj.2019.02.011.Peer-Reviewed Original Research
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 advancesCytoskeleton
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 ResearchDynamin 2 regulation of integrin endocytosis, but not VEGF signaling, is crucial for developmental angiogenesis
Lee MY, Skoura A, Park EJ, Landskroner-Eiger S, Jozsef L, Luciano AK, Murata T, Pasula S, Dong Y, Bouaouina M, Calderwood DA, Ferguson SM, De Camilli P, Sessa WC. Dynamin 2 regulation of integrin endocytosis, but not VEGF signaling, is crucial for developmental angiogenesis. Development 2014, 141: 1465-1472. PMID: 24598168, PMCID: PMC3957370, DOI: 10.1242/dev.104539.Peer-Reviewed Original ResearchConceptsΒ1 integrinFocal adhesion sizeGrowth factor signalingVascular endothelial growth factor signalingEndocytic turnoverIntegrin endocytosisDynamin 2Adhesion sizeFactor signalingDevelopmental angiogenesisAngiogenic sproutingCell migrationCultured endothelial cellsMultiple integrinsInducible lossIntegrinsMorphogenesisActivation stateDNM2Endothelial cellsAngiogenesisVivoEndocytosisSurface levelSignalingIntegrin Cytoplasmic Tail Interactions
Morse EM, Brahme NN, Calderwood DA. Integrin Cytoplasmic Tail Interactions. Biochemistry 2014, 53: 810-820. PMID: 24467163, PMCID: PMC3985435, DOI: 10.1021/bi401596q.Peer-Reviewed Original ResearchConceptsIntegrin-interacting proteinsIntegrin cytoplasmic tailsCell surface adhesion receptorsIntegrin-binding proteinsHeterodimeric cell-surface adhesion receptorsSurface adhesion receptorsExtracellular ligandsMulticellular lifeCytoplasmic tailIntegrin engagementCell motilityExtracellular environmentTransduce chemicalIntegrin activityIntegrin localizationIntracellular proteinsAdhesion receptorsTail interactionsMechanical signalsProteinIntegrinsCellsCytoskeletonLocalizationTraffickingDifferences 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
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 cultureStructural Basis for Small G Protein Effector Interaction of Ras-related Protein 1 (Rap1) and Adaptor Protein Krev Interaction Trapped 1 (KRIT1)
Li X, Zhang R, Draheim KM, Liu W, Calderwood DA, Boggon TJ. Structural Basis for Small G Protein Effector Interaction of Ras-related Protein 1 (Rap1) and Adaptor Protein Krev Interaction Trapped 1 (KRIT1). Journal Of Biological Chemistry 2012, 287: 22317-22327. PMID: 22577140, PMCID: PMC3381192, DOI: 10.1074/jbc.m112.361295.Peer-Reviewed Original ResearchAmino Acid SequenceCrystallography, X-RayGene Expression RegulationGTP PhosphohydrolasesHemangioma, Cavernous, Central Nervous SystemHumansIntegrinsKRIT1 ProteinMicrotubule-Associated ProteinsModels, BiologicalModels, MolecularMolecular Sequence DataMutagenesisPoint MutationProtein ConformationProtein Interaction MappingProtein Structure, TertiaryProto-Oncogene ProteinsRap1 GTP-Binding ProteinsSequence Homology, Amino AcidSignal TransductionFunctional differences between kindlin-1 and kindlin-2 in keratinocytes
Bandyopadhyay A, Rothschild G, Kim S, Calderwood DA, Raghavan S. Functional differences between kindlin-1 and kindlin-2 in keratinocytes. Journal Of Cell Science 2012, 125: 2172-2184. PMID: 22328497, PMCID: PMC3367939, DOI: 10.1242/jcs.096214.Peer-Reviewed Original ResearchConceptsFocal adhesionsKindlin-2Kindlin-1Cell spreadingPeripheral focal adhesionsIntegrin β1Wild-type cellsUnexpected functional consequencesIntegrin β6Wild-type keratinocytesCytoplasmic tailNull keratinocytesKindlinNull cellsFunctional consequencesDirect interactionFunctional differencesUnique functionRelated integrinsIntegrinsCellsAdhesionKeratinocytesIntegrin αvβ6KnockdownFilamin 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 remodelingNanopatterning 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
Functional and Structural Insights into ASB2α, a Novel Regulator of Integrin-dependent Adhesion of Hematopoietic Cells*
Lamsoul I, Burande CF, Razinia Z, Houles TC, Menoret D, Baldassarre M, Erard M, Moog-Lutz C, Calderwood DA, Lutz PG. Functional and Structural Insights into ASB2α, a Novel Regulator of Integrin-dependent Adhesion of Hematopoietic Cells*. Journal Of Biological Chemistry 2011, 286: 30571-30581. PMID: 21737450, PMCID: PMC3162417, DOI: 10.1074/jbc.m111.220921.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid MotifsAnimalsCarrier ProteinsCell AdhesionFibronectinsGene Expression RegulationHeLa CellsHematopoietic Stem CellsHumansIntegrinsMiceMusclesNIH 3T3 CellsProtein BindingProtein Structure, TertiarySubstrate SpecificitySuppressor of Cytokine Signaling ProteinsConceptsN-terminal regionHematopoietic cellsE3 ubiquitin ligase complexE3 ubiquitin ligase functionShort N-terminal regionUbiquitin ligase complexUbiquitin ligase functionAcid-responsive genesIntegrin-dependent adhesionRetinoic acid-responsive geneCell fateLigase complexSpecificity subunitLigase functionResponsive genesLeukemia cellsProteasomal degradationNovel regulatorFilamin A.Myogenic differentiationStructural insightsASB2αΒ-integrinAcute promyelocytic leukemia cellsStructural homologyTalin 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