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 adhesionMonocytesInflammationNanoscopy reveals integrin clustering reliant on kindlin-3 but not talin-1
Wu Y, Cao Z, Liu W, Cahoon J, Wang K, Wang P, Hu L, Chen Y, Moser M, Vella A, Ley K, Wen L, Fan Z. Nanoscopy reveals integrin clustering reliant on kindlin-3 but not talin-1. Cell Communication And Signaling 2025, 23: 12. PMID: 39773732, PMCID: PMC11707915, DOI: 10.1186/s12964-024-02024-8.Peer-Reviewed Original Research
2024
Mechanosensing regulates tissue repair program in macrophages
Meizlish M, Kimura Y, Pope S, Matta R, Kim C, Philip N, Meyaard L, Gonzalez A, Medzhitov R. Mechanosensing regulates tissue repair program in macrophages. Science Advances 2024, 10: eadk6906. PMID: 38478620, PMCID: PMC10936955, DOI: 10.1126/sciadv.adk6906.Peer-Reviewed Original ResearchConceptsExtracellular matrixRegulate chromatin accessibilityTissue repair programGene expression programsCytoskeletal dynamicsChromatin accessibilityAmoeboid migrationCytoskeletal remodelingBiochemical signalsTissue homeostasisExpression programsColony-stimulating factor-1Tissue-resident macrophagesFactor 1MechanosensingRegulating tissue repairTissue integrityMacrophagesTissueThree-dimensional environmentRepair programHomeostasis
2023
Altered Integrin Signaling in Thoracic Aortopathy
Humphrey J, Schwartz M. Altered Integrin Signaling in Thoracic Aortopathy. Arteriosclerosis Thrombosis And Vascular Biology 2023, 43: 1154-1156. PMID: 37165879, DOI: 10.1161/atvbaha.123.319404.Commentaries, Editorials and LettersCell-matrix interactions control biliary organoid polarity, architecture, and differentiation
Fiorotto R, Mariotti V, Taleb S, Zehra S, Nguyen M, Amenduni M, Strazzabosco M. Cell-matrix interactions control biliary organoid polarity, architecture, and differentiation. Hepatology Communications 2023, 7: e0094. PMID: 36972396, PMCID: PMC10503667, DOI: 10.1097/hc9.0000000000000094.Peer-Reviewed Original ResearchConceptsBiliary organoidsNovel organoid modelImmune cell typesOrganotypic culture systemProinflammatory chemokinesStem cell featuresBiliary epitheliumExtracellular matrixEpithelial permeabilityImportant causeBile acidsBiliary differentiationBile transportHuman liverOrganoid modelsDisease modelsCholangiopathyCell featuresTight junctionsLiverCell typesInternal lumenOrganoidsSingle-cell transcriptomicsPathogenic bacteriaGenetic Variants in ARHGEF6 Cause Congenital Anomalies of the Kidneys and Urinary Tract in Humans, Mice, and Frogs
Klämbt V, Buerger F, Wang C, Naert T, Richter K, Nauth T, Weiss A, Sieckmann T, Lai E, Connaughton D, Seltzsam S, Mann N, Majmundar A, Wu C, Onuchic-Whitford A, Shril S, Schneider S, Schierbaum L, Dai R, Bekheirnia M, Joosten M, Shlomovitz O, Vivante A, Banne E, Mane S, Lifton R, Kirschner K, Kispert A, Rosenberger G, Fischer K, Lienkamp S, Zegers M, Hildebrandt F. Genetic Variants in ARHGEF6 Cause Congenital Anomalies of the Kidneys and Urinary Tract in Humans, Mice, and Frogs. Journal Of The American Society Of Nephrology 2023, 34: 273-290. PMID: 36414417, PMCID: PMC10103091, DOI: 10.1681/asn.2022010050.Peer-Reviewed Original ResearchConceptsIntegrin-linked kinaseFocal adhesion proteinsThree-dimensional (3D) MadinCdc42/Rac1Genetic variantsRac1/Cdc42Loss of interactionFrog modelPolarity defectsExchange factorNovel genesFocal adhesionsLamellipodia formationARHGEF6Adhesion proteinsDisease genesDeleterious variantsCell spreadingLumen formationCell migrationGenesProteinHemizygous variantKidney cellsExome sequencingUse 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 integrinsΒ5TailMutagenesisIntegrin Conformational Dynamics and Mechanotransduction
Kolasangiani R, Bidone T, Schwartz M. Integrin Conformational Dynamics and Mechanotransduction. Cells 2022, 11: 3584. PMID: 36429013, PMCID: PMC9688440, DOI: 10.3390/cells11223584.Peer-Reviewed Original ResearchConceptsCell-cell adhesionCell-extracellular matrixExtracellular ligandsIntegrin affinityConformational dynamicsIntegrin familyConformational statesConformational transitionTissue integrityCell functionCentral mediatorRemarkable convergenceMechanical forcesForce transmissionCytoskeletonMechanotransductionAdhesionFirm adhesionUnanswered questionsIntegrinsNew informationPathwayLigandsUterine administration of C-X-C motif chemokine ligand 12 increases the pregnancy rates in mice with induced endometriosis
Rosa-E-Silva ACJS, Mamillapalli R, Rosa-E-Silva JC, Ucar A, Schwartz J, Taylor HS. Uterine administration of C-X-C motif chemokine ligand 12 increases the pregnancy rates in mice with induced endometriosis. F&S Science 2022, 4: 65-73. PMID: 36252793, DOI: 10.1016/j.xfss.2022.10.003.Peer-Reviewed Original ResearchConceptsC motif chemokine ligand 12Endometriosis groupPregnancy rateChemokine ligand 12Alpha v beta 3 integrinUterine injectionBeta 3 integrinBMDC recruitmentProgesterone receptorMouse modelBone marrow-derived cell recruitmentHigher cumulative pregnancy rateLigand 12Therapeutic agentsEndometrial receptivity defectsCumulative pregnancy rateEndometrial receptivity markersSham surgery groupBone marrow transplantationLower pregnancy ratesAcademic medical centerPotential therapeutic agentReceptivity markersSurgery groupInduced endometriosisOrganization, 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 understandingRabphilin3A reduces integrin-dependent growth cone signaling to restrict axon regeneration after trauma
Sekine Y, Kannan R, Wang X, Strittmatter SM. Rabphilin3A reduces integrin-dependent growth cone signaling to restrict axon regeneration after trauma. Experimental Neurology 2022, 353: 114070. PMID: 35398339, PMCID: PMC9555232, DOI: 10.1016/j.expneurol.2022.114070.Peer-Reviewed Original ResearchConceptsAxon regenerationModerate spinal cord contusion injurySpinal cord contusion injuryTraumatic spinal cord injuryAdult mammalian central nervous systemGrowth conesRetinal ganglion cell axonsOptic nerve crushSpinal cord crush injuryGanglion cell axonsSpinal cord injuryMammalian central nervous systemCentral nervous systemCorticospinal axon regenerationContusion injuryAxonal sproutingCrush injuryNerve crushAxonal growth conesCord injuryAxon sproutingCell axonsProximal bodyNervous systemNeural repairDevelopment of Tbet- and CD11c-expressing B cells in a viral infection requires T follicular helper cells outside of germinal centers
Song W, Antao OQ, Condiff E, Sanchez GM, Chernova I, Zembrzuski K, Steach H, Rubtsova K, Angeletti D, Lemenze A, Laidlaw BJ, Craft J, Weinstein JS. Development of Tbet- and CD11c-expressing B cells in a viral infection requires T follicular helper cells outside of germinal centers. Immunity 2022, 55: 290-307.e5. PMID: 35090581, PMCID: PMC8965751, DOI: 10.1016/j.immuni.2022.01.002.Peer-Reviewed Original ResearchConceptsFollicular helper cellsB cellsGC B cellsHelper cellsMemory subsetsRobust recall responsesB cell subsetsGerminal center formationB cell generationAcute infectionCell subsetsRecall responsesTh1 cellsProximal deliveryCD11cGerminal centersIntegrin LFA-1Viral infectionAntibody productionVLA-4Splenic retentionLFA-1TbetBCL6 expressionInfection
2021
Talin in mechanotransduction and mechanomemory at a glance
Goult BT, Brown NH, Schwartz MA. Talin in mechanotransduction and mechanomemory at a glance. Journal Of Cell Science 2021, 134: jcs258749. PMID: 34708856, PMCID: PMC8697387, DOI: 10.1242/jcs.258749.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesIntegrinsMechanotransduction, CellularProtein BindingSignal TransductionTalinConceptsHelical bundleHead domainC-terminal rod domainIntegrin conformational activationCytoskeletal linker proteinTerminal head domainExtracellular matrix proteinsCryptic binding sitesFlexible neck regionGlance articleAccompanying posterLinker proteinCytoplasmic tailConformational activationRod domainActin filamentsMatrix proteinsCell scienceTalinProteinBinding sitesDomain linksForce inducesDomainMechanotransductionIntegrin-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 ResearchMeSH KeywordsCell AdhesionIntegrin alphaVbeta3IntegrinsLigandsMechanical PhenomenaProtein BindingTalinConceptsCellular 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 informationDifferential Integrin Adhesome Expression Defines Human NK Cell Residency and Developmental Stage.
Hegewisch-Solloa E, Seo S, Mundy-Bosse BL, Mishra A, Waldman EH, Maurrasse S, Grunstein E, Connors TJ, Freud AG, Mace EM. Differential Integrin Adhesome Expression Defines Human NK Cell Residency and Developmental Stage. The Journal Of Immunology 2021, 207: 950-965. PMID: 34282002, PMCID: PMC8324558, DOI: 10.4049/jimmunol.2100162.Peer-Reviewed Original ResearchConceptsActin regulating proteinsDevelopmental stagesNK cellsCell developmental stagesHuman hematopoietic precursorsActin homeostasisPeripheral bloodSignaling interactionsHuman NK cell populationsMolecular networksExpression profilesDifferential expressionNK cell populationVaried microenvironmentsInnate immune cellsRegulating proteinsVariety of microenvironmentsHematopoietic precursorsAdhesomeActin contentCell coculture systemCell populationsImmune cellsExpressionProteinMechanistic basis of post-treatment control of SIV after anti-α4β7 antibody therapy
Wells CR, Cao Y, Durham DP, Byrareddy SN, Ansari AA, Ruddle NH, Townsend JP, Galvani AP, Perelson AS. Mechanistic basis of post-treatment control of SIV after anti-α4β7 antibody therapy. PLOS Computational Biology 2021, 17: e1009031. PMID: 34106916, PMCID: PMC8189501, DOI: 10.1371/journal.pcbi.1009031.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyViral loadPost-treatment controlAnti-α4β7 antibodyViral remissionAntibody treatmentViral controlCombinations of cARTImmune effector cell responsesPost-treatment viral controlSIV RNA copies/Depletion of CD8Ongoing immune responseEarly SIV infectionRNA copies/Stable viral loadEffector cell responsesViral load dataDifferent viral loadsAbsence of treatmentSubset of animalsNonhuman primate experimentsDifferent primary mechanismsLongitudinal viral load dataCART cessationIntegrin 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 measurementsIntegrinsThe LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation
Carley E, Stewart R, Zieman AG, Jalilian I, King DE, Zubek AE, Lin S, Horsley V, King MC. The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation. ELife 2021, 10: e58541. PMID: 33779546, PMCID: PMC8051949, DOI: 10.7554/elife.58541.Peer-Reviewed Original ResearchConceptsCell fateEpidermal cell fateLinker of nucleoskeletonCell fate decisionsEpidermal differentiation genesEpidermal differentiationDirect force transmissionEpidermal stem cellsCytoskeleton (LINC) complexLINC complexFate decisionsNuclear laminaType laminsDifferentiation genesIntegrin engagementForce transductionDifferentiation concomitantChemical signalsMechanotransduction pathwaysKeratinocyte progenitorsMolecular biosensorsStem cellsKeratinocyte differentiationDifferentiationMechanical input
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