2025
CFTR dictates monocyte adhesion by facilitating integrin clustering but not activation
Younis D, Marosvari M, Liu W, Pulikkot S, Cao Z, Zhou B, Vella A, McArdle S, Hu L, Chen Y, Gan W, Yu J, Bruscia E, Fan Z. CFTR dictates monocyte adhesion by facilitating integrin clustering but not activation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2412717122. PMID: 39813254, PMCID: PMC11760921, DOI: 10.1073/pnas.2412717122.Peer-Reviewed Original ResearchConceptsIntegrin clusteringCF transmembrane conductance regulatorCystic fibrosisAdhesion defectsPathogenesis of cystic fibrosisClinically relevant disease modelsMembrane recruitmentTransmembrane conductance regulatorIntegrin activationTherapeutic strategy designRelevant disease modelsIntegrinCF monocytesCell adhesionMonocyte dysfunctionPatients' monocytesTissue infectionsConductance regulatorSuperresolution microscopyCortex formationLeukocyte-dependent inflammationInflammatory pathogenesisLeukocyte adhesionMonocytesInflammation
2021
Integrin-based mechanosensing through conformational deformation
Driscoll TP, Bidone TC, Ahn SJ, Yu A, Groisman A, Voth GA, Schwartz MA. Integrin-based mechanosensing through conformational deformation. Biophysical Journal 2021, 120: 4349-4359. PMID: 34509509, PMCID: PMC8553792, DOI: 10.1016/j.bpj.2021.09.010.Peer-Reviewed Original ResearchConceptsCellular mechanosensingFocal adhesion kinase activationIntegrin conformational activationLarge-scale conformational transitionsWild-type integrinIntegrin mutantsEmbryonic developmentConformational activationCellular stiffnessHigh-affinity stateKinase activationSubstrate stiffnessBiological processesIntegrin activationCell spreadingMutantsIntegrin conformationTraction stressConformational deformationConformational transitionIntegrinsMechanosensingSoluble ligandsAffinity stateMolecular-level informationMitofusin-2 regulates leukocyte adhesion and β2 integrin activation
Liu W, Hsu AY, Wang Y, Lin T, Sun H, Pachter JS, Groisman A, Imperioli M, Yungher FW, Hu L, Wang P, Deng Q, Fan Z. Mitofusin-2 regulates leukocyte adhesion and β2 integrin activation. Journal Of Leukocyte Biology 2021, 111: 771-791. PMID: 34494308, PMCID: PMC8901796, DOI: 10.1002/jlb.1a0720-471r.Peer-Reviewed Original ResearchConceptsΒ2 integrin activationIntegrin activationMitofusin 2Mfn2 deficiencyConformation-specific monoclonal antibodiesMFN2 knockdownHL60 cellsNeutrophil-like HL60 cellsMolecular detailsActin polymerizationCell spreadingAdhesion defectsReduced expressionInnate immunityKnockdownNew insightsActivationCellsLeukocyte adhesionAdhesionCell rollingCrucial stepMonoclonal antibodiesDifferentiationVascular endotheliumIntegrin intra-heterodimer affinity inversely correlates with integrin activatability
Sun G, Guillon E, Holley SA. Integrin intra-heterodimer affinity inversely correlates with integrin activatability. Cell Reports 2021, 35: 109230. PMID: 34107244, PMCID: PMC8227800, DOI: 10.1016/j.celrep.2021.109230.Peer-Reviewed Original ResearchConceptsFluorescence cross-correlation spectroscopyCell surface expressionHeterodimeric cell surface receptorsPoor cell surface expressionCell surface stabilityRobust cell surface expressionExtracellular matrix proteinsCell surface receptorsZebrafish somitogenesisSurface expressionCross-correlation spectroscopyFluorescence resonance energy transferIntegrin activationΒ-subunitIntegrin heterodimersFibronectin matrixMatrix proteinsVivo contextConformational changesCell adhesionResonance energy transferSurface receptorsIntegrin αvβ1Biophysical measurementsIntegrinsMitofusin‐2 regulates leukocyte adhesion through the maturation of β2 integrin activation in differentiation
Fan Z, Liu W, Wang Y, Hsu A, Lin T, Sun H, Pachter J, Groisman A, Imperioli M, Yungher F, Hu L, Wang P, Deng Q. Mitofusin‐2 regulates leukocyte adhesion through the maturation of β2 integrin activation in differentiation. The FASEB Journal 2021, 35 DOI: 10.1096/fasebj.2021.35.s1.00211.Peer-Reviewed Original ResearchΒ2 integrin activationNeutrophil adhesionLeukocyte adhesionMitofusin 2HL60 cellsIntegrin activationNeutrophil recruitmentNeutrophil-like HL60 cellsVascular endotheliumFMLP receptorInnate immunityReduced expressionΒ2 integrinsConformational specific antibodiesMitofusin 2 deficiencyActivationCellsMaturationCD35InflammationNeutrophilsEndotheliumDiseaseΒ2Immunity
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 toolExocytosisOrganismsVesiclesPKN1 Directs Polarized RAB21 Vesicle Trafficking via RPH3A and Is Important for Neutrophil Adhesion and Ischemia-Reperfusion Injury
Yuan Q, Ren C, Xu W, Petri B, Zhang J, Zhang Y, Kubes P, Wu D, Tang W. PKN1 Directs Polarized RAB21 Vesicle Trafficking via RPH3A and Is Important for Neutrophil Adhesion and Ischemia-Reperfusion Injury. Cell Reports 2017, 19: 2586-2597. PMID: 28636945, PMCID: PMC5548392, DOI: 10.1016/j.celrep.2017.05.080.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCell AdhesionCell PolarityFemaleKidneyMaleMice, Inbred C57BLMice, TransgenicNerve Tissue ProteinsNeutrophilsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Protein Kinase CProtein Processing, Post-TranslationalProtein Transportrab GTP-Binding ProteinsReperfusion InjuryTransendothelial and Transepithelial MigrationTransport VesiclesVesicular Transport ProteinsConceptsTissue injuryNeutrophil adhesionRenal ischemia-reperfusion modelEndothelial cellsDecrease tissue injuryMyeloid-specific lossIschemia-reperfusion injuryIschemia-reperfusion modelInnate immune responseNeutrophil integrin activationInflammatory modelInflammatory responseImmune responseTherapeutic interventionsInjuryNeutrophilsRPH3AIntegrin activationCells
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 ResearchThe fibronectin III-1 domain activates a PI3-Kinase/Akt signaling pathway leading to αvβ5 integrin activation and TRAIL resistance in human lung cancer cells
Cho C, Horzempa C, Jones D, McKeown-Longo PJ. The fibronectin III-1 domain activates a PI3-Kinase/Akt signaling pathway leading to αvβ5 integrin activation and TRAIL resistance in human lung cancer cells. BMC Cancer 2016, 16: 574. PMID: 27484721, PMCID: PMC4970220, DOI: 10.1186/s12885-016-2621-6.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungCaspase 8Cell Line, TumorCell SurvivalDrug Resistance, NeoplasmFibronectin Type III DomainFibronectinsGene Expression Regulation, NeoplasticHumansLung NeoplasmsPhosphatidylinositol 3-KinasesProtein FoldingProto-Oncogene Proteins c-aktReceptors, VitronectinSignal TransductionTNF-Related Apoptosis-Inducing LigandVitronectinConceptsType III domainLung cancer cellsUnfolded domainsTRAIL resistancePI3-kinase/AktSerine/threonine kinase pathwaysCancer cellsMulti-modular proteinThreonine kinase pathwaysNCI-H460 lung cancer cellsFnIII-1cFirst Type III domainNon-small cell lung cancer cellsTRAIL-induced apoptosisΑvβ5 integrin receptorLung cancer resistanceCell lung cancer cellsHuman lung cancer cellsKinase pathwayCancer cell resistanceIntegrin activationCaspase-8Signaling pathwaysFibronectin matrixSensitive proteins
2015
Cross-Scale Integrin Regulation Organizes ECM and Tissue Topology
Jülich D, Cobb G, Melo AM, McMillen P, Lawton AK, Mochrie SG, Rhoades E, Holley SA. Cross-Scale Integrin Regulation Organizes ECM and Tissue Topology. Developmental Cell 2015, 34: 33-44. PMID: 26096733, PMCID: PMC4496283, DOI: 10.1016/j.devcel.2015.05.005.Peer-Reviewed Original ResearchConceptsExtracellular matrixCadherin-2Integrin α5Cell-cell adhesionFluorescence cross-correlation spectroscopyECM protein fibronectinSomite boundariesCross-correlation spectroscopyAdjacent cell membranesBody elongationECM assemblyIntegrin associationIntegrin activationPhysical associationActive conformationFibronectin fibrillogenesisProtein fibronectinTissue assemblyIntegrin conformationTissue topologyInactive integrinsCell membraneCross-scale mechanismsStereotypic patternAnimal tissuesThe regulatory role of serum response factor pathway in neutrophil inflammatory response
Taylor A, Halene S. The regulatory role of serum response factor pathway in neutrophil inflammatory response. Current Opinion In Hematology 2015, 22: 67-73. PMID: 25402621, PMCID: PMC4374983, DOI: 10.1097/moh.0000000000000099.Peer-Reviewed Original ResearchConceptsSerum response factor pathwayRole of SRFLinear actin polymerizationEssential transcription factorCell-cell interactionsRas homolog family memberAberrant myeloid differentiationFactor pathwayT cell developmentActin cytoskeletonMultiple complex rolesRegulated processSRF pathwayTranscription factorsDiaphanous 1Actin polymerizationMyeloid cell functionChromosome 5Integrin activationIntegrin complexRegulatory roleMyeloid differentiationCommon genetic aberrationsLeukocyte adhesion deficiencyAdaptive immune system
2014
SRF is required for neutrophil migration in response to inflammation
Taylor A, Tang W, Bruscia EM, Zhang PX, Lin A, Gaines P, Wu D, Halene S. SRF is required for neutrophil migration in response to inflammation. Blood 2014, 123: 3027-3036. PMID: 24574460, PMCID: PMC4014845, DOI: 10.1182/blood-2013-06-507582.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActinsAnimalsBlotting, WesternCell AdhesionCell MovementChemokinesGene ExpressionInflammationIntegrinsMiceMice, KnockoutMice, TransgenicMicroscopy, ConfocalNeutrophilsN-Formylmethionine Leucyl-PhenylalaninePolymerizationReverse Transcriptase Polymerase Chain ReactionSerum Response FactorSignal TransductionConceptsKO neutrophilsNeutrophil functionNormal neutrophil numbersSerum response factorSites of inflammationRole of SRFLoss of SRFNeutrophil numbersNeutrophil migrationMalignant processNeutrophilsCytokine stimuliChemokine gradientsCell functionExpression levelsIntegrin expression levelsInflammationMicePrimary defenseMegakaryocyte maturationNormal cell functionVivoCellular adhesionMaster regulatorIntegrin activationPodocyte-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 tailsβ1 integrin regulates Arg to promote invadopodial maturation and matrix degradation
Beaty BT, Sharma VP, Bravo-Cordero JJ, Simpson MA, Eddy RJ, Koleske AJ, Condeelis J. β1 integrin regulates Arg to promote invadopodial maturation and matrix degradation. Molecular Biology Of The Cell 2013, 24: 1661-1675. PMID: 23552693, PMCID: PMC3667720, DOI: 10.1091/mbc.e12-12-0908.Peer-Reviewed Original ResearchMeSH KeywordsActin Depolymerizing FactorsActinsCell Line, TumorCell MovementCortactinExtracellular MatrixGene Expression Regulation, NeoplasticHumansIntegrin beta1PhosphorylationProtein BindingProtein MultimerizationProtein-Tyrosine KinasesPseudopodiaRNA, Small InterferingSignal TransductionTyrosineConceptsΒ1 integrinBarbed end formationInvasive membrane protrusionsMatrix degradationΒ1 integrin activationMature invadopodiaInvadopodial functionMetastatic human breast cancer cellsMembrane protrusionsExtracellular matrix degradationCortactin phosphorylationTyrosine 421InvadopodiaIntegrin activationMatrix proteolysisHuman breast cancer cellsThree-dimensional matrixPrecursor maturationBreast cancer cellsMetastatic tumor cellsIntegrinsCancer cellsPhosphorylationMaturationFundamental role
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 motif
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