2025
High-content image-based pooled screens reveal regulators of synaptogenesis
Le A, Biederer T, Blainey P. High-content image-based pooled screens reveal regulators of synaptogenesis. Cell Reports 2025, 44: 115889. PMID: 40560725, DOI: 10.1016/j.celrep.2025.115889.Peer-Reviewed Original ResearchNeuroligin-1High-content screening approachPresynaptic assemblyCell-cell interactionsCytoskeletal dynamicsRegulation of synaptogenesisPhosphatase PTENPooled screeningSynapse inductionCell adhesionSynapse formationSynapse typesScreening platformPhenotypic profileDAG1Adhesion moleculesMolecular interactionsScreening approachSynaptogenesisRegulationSynapseNeuroliginInhibitory synapsesNervous systemPTENDecoding Extracellular Protein Glycosylation in Human Health and Disease
Steigmeyer A, Lowery S, Rangel-Angarita V, Malaker S. Decoding Extracellular Protein Glycosylation in Human Health and Disease. Annual Review Of Analytical Chemistry 2025, 18: 241-264. PMID: 39813736, DOI: 10.1146/annurev-anchem-071024-124203.Peer-Reviewed Original ResearchPost-translational modificationsProtein glycosylationStudy protein glycosylationHeterogeneous post-translational modificationsBiologically relevant contextProtein foldingGlycan complexityNontemplated natureCell adhesionAberrant glycosylationProtein backboneGlycosylationBiochemical processesProteinGlycoprotein characterizationCovalent attachmentHealth and DiseaseGlycansStructural heterogeneityHuman healthRelevant contextGlycoproteinFoldingBiologyN-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
2024
Substrate geometry and topography induce F-actin reorganization and chiral alignment in an adherent model cortex
Sakamoto R, Murrell M. Substrate geometry and topography induce F-actin reorganization and chiral alignment in an adherent model cortex. Cell Reports Physical Science 2024, 5: 102338. DOI: 10.1016/j.xcrp.2024.102338.Peer-Reviewed Original ResearchF-actin organizationF-actin networkF-actinF-actin reorganizationSubstrate featuresActin cortexCytoskeletal organizationGiant unilamellar vesiclesIntracellular signalingCell adhesionGeometry sensingLiposome shapeCell membraneMembrane deformationUnilamellar vesiclesAdherent liposomeCellsActinOrganizationVesiclesAdhesionLiposomesDantrolene corrects cellular disease features of Darier disease and may be a novel treatment
Hunt M, Wang N, Pupinyo N, Curman P, Torres M, Jebril W, Chatzinikolaou M, Lorent J, Silberberg G, Bansal R, Burner T, Zhou J, Kimeswenger S, Hoetzenecker W, Choate K, Bachar-Wikstrom E, Wikstrom J. Dantrolene corrects cellular disease features of Darier disease and may be a novel treatment. EMBO Molecular Medicine 2024, 16: 1986-2001. PMID: 39060641, PMCID: PMC11392931, DOI: 10.1038/s44321-024-00104-3.Peer-Reviewed Original ResearchDarier's diseaseER stressCell adhesionER calcium levelsUpregulation of ER stressInhibited calcium releaseRyanodine receptor antagonistEndoplasmic reticulum calcium homeostasisTarget pathogenic mechanismsFeatures of Darier's diseaseIdentified dysregulated genesMechanisms of DDNon-dermatological indicationsCellular calcium dynamicsCellular functionsER calciumHomeostasis pathwaysATP2A2 geneIn vitro modelReceptor antagonistPumps calciumCalcium releasePromote cell adhesionIsoform 2Suppressed apoptosis
2023
Bulk and single-nucleus RNA sequencing highlight immune pathways induced in individuals during an Ixodes scapularis tick bite
Tang X, Lynn G, Cui Y, Cerny J, Arora G, Tomayko M, Craft J, Fikrig E. Bulk and single-nucleus RNA sequencing highlight immune pathways induced in individuals during an Ixodes scapularis tick bite. Infection And Immunity 2023, 91: e00282-23. PMID: 37846980, PMCID: PMC10652856, DOI: 10.1128/iai.00282-23.Peer-Reviewed Original ResearchConceptsRNA sequencingSingle-nucleus RNA sequencingBulk RNA sequencingInterleukin-17 signalingPlatelet activation pathwaysLaboratory guinea pigsSnRNA-seqHippo signalingIndividual genesPeripheral bloodTick biteAdaptive immunityAnti-tick vaccinesGuidance pathwayImmune pathwaysNew biomarkersHost responseGuinea pigsHematophagous arthropodsHost defenseCell adhesionTick attachmentNovel insightsTick feedingPhysiological consequencesInositol hexakisphosphate kinase 1 is essential for cell junction integrity in the mouse seminiferous epithelium
Bhat S, Malla A, Oddi V, Sen J, Bhandari R. Inositol hexakisphosphate kinase 1 is essential for cell junction integrity in the mouse seminiferous epithelium. Biochimica Et Biophysica Acta (BBA) - Molecular Cell Research 2023, 1871: 119596. PMID: 37742721, DOI: 10.1016/j.bbamcr.2023.119596.Peer-Reviewed Original ResearchConceptsBlood-testis barrierSeminiferous epitheliumBlood-testis barrier disruptionMouse seminiferous epitheliumCell adhesionGerm cell adhesionActin-based cytoskeletonInositol hexakisphosphate kinase 1Inositol hexakisphosphate kinasesGerm cell lossDownregulation of transcriptsMammalian testisKnockout miceRound spermatidsSertoli cellsSubcellular mislocalizationCofilin dephosphorylationIntegrin signalingMouse testisTight junction protein claudin-3Transcriptional misregulationGap junction protein connexinCell junction integrityIP6K1Junction protein connexinMettl3-catalyzed m6A regulates histone modifier and modification expression in self-renewing somatic tissue
López A, Ko E, Huang S, Pacella G, Kuprasertkul N, D’souza C, Hueros R, Shen H, Stoute J, Elashal H, Sinkfield M, Anderson A, Prouty S, Li H, Seykora J, Liu K, Capell B. Mettl3-catalyzed m6A regulates histone modifier and modification expression in self-renewing somatic tissue. Science Advances 2023, 9: eadg5234. PMID: 37656787, PMCID: PMC10854438, DOI: 10.1126/sciadv.adg5234.Peer-Reviewed Original ResearchConceptsSomatic tissuesMessenger RNALayer of gene regulationHistone modifying enzymesImpaired cell adhesionChromatin modifiersGene regulationAbundant modificationGene expression abnormalitiesHistone modifiersSelf-renewalMethyltransferase-like protein 3Gross phenotypic abnormalitiesModifying enzymesN6</i>-methyladenosineEpithelial developmentCell adhesionPhenotypic abnormalitiesHair follicle morphogenesisProgenitors in vivoProtein 3Expression abnormalitiesOral ulcersEpithelial tissuesFollicle morphogenesisMice lacking Ptprd exhibit deficits in goal-directed behavior and female-specific impairments in sensorimotor gating
Ho E, Welch A, Thompson S, Knowles J, Dulawa S. Mice lacking Ptprd exhibit deficits in goal-directed behavior and female-specific impairments in sensorimotor gating. PLOS ONE 2023, 18: e0277446. PMID: 37205689, PMCID: PMC10198499, DOI: 10.1371/journal.pone.0277446.Peer-Reviewed Original ResearchConceptsProtein tyrosine phosphatase receptor type DGenome-wide association studiesProtein tyrosine phosphatase familyTyrosine phosphatase familyReceptor type DPhosphatase familyAssociation studiesGenetic studiesCell adhesionPTPRDNest-building behaviorEffect of genotypeSynaptic specificationNeuropsychiatric phenotypesTraitsConstitutive lackKnockout miceKO miceGatingLociBuilding behaviorMicePhenotypeUse 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 fashionCells
2021
Integrin 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 measurementsIntegrinsESDN inhibits melanoma progression by blocking E-selectin expression in endothelial cells via STAT3
Coppo R, Orso F, Virga F, Dalmasso A, Baruffaldi D, Nie L, Clapero F, Dettori D, Quirico L, Grassi E, Defilippi P, Provero P, Valdembri D, Serini G, Sadeghi MM, Mazzone M, Taverna D. ESDN inhibits melanoma progression by blocking E-selectin expression in endothelial cells via STAT3. Cancer Letters 2021, 510: 13-23. PMID: 33862151, PMCID: PMC8581997, DOI: 10.1016/j.canlet.2021.04.005.Peer-Reviewed Original ResearchSynaptic processes and immune-related pathways implicated in Tourette syndrome
Tsetsos F, Yu D, Sul JH, Huang AY, Illmann C, Osiecki L, Darrow SM, Hirschtritt ME, Greenberg E, Muller-Vahl KR, Stuhrmann M, Dion Y, Rouleau GA, Aschauer H, Stamenkovic M, Schlögelhofer M, Sandor P, Barr CL, Grados MA, Singer HS, Nöthen MM, Hebebrand J, Hinney A, King RA, Fernandez TV, Barta C, Tarnok Z, Nagy P, Depienne C, Worbe Y, Hartmann A, Budman CL, Rizzo R, Lyon GJ, McMahon WM, Batterson JR, Cath DC, Malaty IA, Okun MS, Berlin C, Woods DW, Lee PC, Jankovic J, Robertson MM, Gilbert DL, Brown LW, Coffey BJ, Dietrich A, Hoekstra PJ, Kuperman S, Zinner SH, Wagner M, Knowles JA, Jeremy Willsey A, Tischfield JA, Heiman GA, Cox NJ, Freimer NB, Neale BM, Davis LK, Coppola G, Mathews CA, Scharf JM, Paschou P, Barr C, Batterson J, Berlin C, Budman C, Cath D, Coppola G, Cox N, Darrow S, Davis L, Dion Y, Freimer N, Grados M, Greenberg E, Hirschtritt M, Huang A, Illmann C, King R, Kurlan R, Leckman J, Lyon G, Malaty I, Mathews C, McMahon W, Neale B, Okun M, Osiecki L, Robertson M, Rouleau G, Sandor P, Scharf J, Singer H, Smit J, Sul J, Yu D, Aschauer H, Barta C, Budman C, Cath D, Depienne C, Hartmann A, Hebebrand J, Konstantinidis A, Mathews C, Müller-Vahl K, Nagy P, Nöthen M, Paschou P, Rizzo R, Rouleau G, Sandor P, Scharf J, Schlögelhofer M, Stamenkovic M, Stuhrmann M, Tsetsos F, Tarnok Z, Wolanczyk T, Worbe Y, Brown L, Cheon K, Coffey B, Dietrich A, Fernandez T, Garcia-Delgar B, Gilbert D, Grice D, Hagstrøm J, Hedderly T, Heiman G, Heyman I, Hoekstra P, Huyser C, Kim Y, Kim Y, King R, Koh Y, Kook S, Kuperman S, Leventhal B, Madruga-Garrido M, Mir P, Morer A, Münchau A, Plessen K, Roessner V, Shin E, Song D, Song J, Tischfield J, Willsey A, Zinner S, Aschauer H, Barr C, Barta C, Batterson J, Berlin C, Brown L, Budman C, Cath D, Coffey B, Coppola G, Cox N, Darrow S, Davis L, Depienne C, Dietrich A, Dion Y, Fernandez T, Freimer N, Gilbert D, Grados M, Greenberg E, Hartmann A, Hebebrand J, Heiman G, Hirschtritt M, Hoekstra P, Huang A, Illmann C, Jankovic J, King R, Kuperman S, Lee P, Lyon G, Malaty I, Mathews C, McMahon W, Müller-Vahl K, Nagy P, Neale B, Nöthen M, Okun M, Osiecki L, Paschou P, Rizzo R, Robertson M, Rouleau G, Sandor P, Scharf J, Schlögelhofer M, Singer H, Stamenkovic M, Stuhrmann M, Sul J, Tarnok Z, Tischfield J, Tsetsos F, Willsey A, Woods D, Worbe Y, Yu D, Zinner S. Synaptic processes and immune-related pathways implicated in Tourette syndrome. Translational Psychiatry 2021, 11: 56. PMID: 33462189, PMCID: PMC7814139, DOI: 10.1038/s41398-020-01082-z.Peer-Reviewed Original ResearchConceptsLigand-gated ion channelsGene setsCell adhesionGenome-wide analysisComplex genetic architectureGenome-wide genotypic dataIon channelsSet of genesIndividual-level genotype dataSignificant gene setsAncestry-matched controlsParticular cell typeGenetic architectureImmune-related pathwaysSignaling processesGenotypic dataMAGMA analysisGenotype dataCell typesGenesIndication of involvementTS pathogenesisAdhesion moleculesGlial functionNew insightsZinc-Dependent Regulation of ZEB1 and YAP1 Coactivation Promotes Epithelial-Mesenchymal Transition Plasticity and Metastasis in Pancreatic Cancer
Liu M, Zhang Y, Yang J, Zhan H, Zhou Z, Jiang Y, Shi X, Fan X, Zhang J, Luo W, Fung K, Xu C, Bronze M, Houchen C, Li M. Zinc-Dependent Regulation of ZEB1 and YAP1 Coactivation Promotes Epithelial-Mesenchymal Transition Plasticity and Metastasis in Pancreatic Cancer. Gastroenterology 2021, 160: 1771-1783.e1. PMID: 33421513, PMCID: PMC8035249, DOI: 10.1053/j.gastro.2020.12.077.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCation Transport ProteinsCell Line, TumorCell MovementCell PlasticityEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticHumansIntegrin alpha3MiceMicroRNAsNeoplasm InvasivenessNeoplasm MetastasisPancreatic NeoplasmsSignal TransductionSpheroids, CellularTranscription FactorsYAP-Signaling ProteinsZincZinc Finger E-box-Binding Homeobox 1ConceptsEMT plasticityHuman pancreatic cancer cellsPancreatic cancer cellsZinc-dependent regulationHippo pathway effector YAP1Cancer cellsMiR-373Zinc transporter ZIP4Potent transcriptional coactivatorMesenchymal-epithelial transition (MET) statesAssociate domainTranscriptional regulationChromatin immunoprecipitationEffector YAP1Transcriptional coactivatorYAP1/Downstream targetsPancreatic cancer metastasisMouse cellsMolecular eventsZIP4YAP1Cell adhesionLuciferase reporterSpontaneous mouse model
2020
Signalling through cerebral cavernous malformation protein networks
Su VL, Calderwood DA. Signalling through cerebral cavernous malformation protein networks. Open Biology 2020, 10: 200263. PMID: 33234067, PMCID: PMC7729028, DOI: 10.1098/rsob.200263.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCarrier ProteinsDisease ManagementDisease SusceptibilityGenetic Predisposition to DiseaseHemangioma, Cavernous, Central Nervous SystemHumansIntracellular SpaceMutationProtein BindingProtein Interaction Domains and MotifsProtein Interaction MappingProtein Interaction MapsProtein TransportSignal TransductionConceptsCCM proteinsCerebral cavernous malformationsCell junctionalMEKK3-MEK5Protein complexesAdaptor proteinProtein functionSubcellular localizationCytoskeletal reorganizationComplex proteinsProtein networkRhoA-ROCKMolecular basisProtein activityGene expressionFunction mutationsCell adhesionCell contractilityProteinPathwayLeaky blood vesselsCurrent knowledgeDisease pathologyCdc42Recent advancesMurine Epsins Play an Integral Role in Podocyte Function
Wang Y, Pedigo CE, Inoue K, Tian X, Cross E, Ebenezer K, Li W, Wang Z, Shin JW, Schwartze E, Groener M, Ishibe S. Murine Epsins Play an Integral Role in Podocyte Function. Journal Of The American Society Of Nephrology 2020, 31: 2870-2886. PMID: 33051360, PMCID: PMC7790213, DOI: 10.1681/asn.2020050691.Peer-Reviewed Original ResearchConceptsSerum response factorPodocyte-specific lossCell division control protein 42 homologCell adhesionRegulation of Cdc42Integrin expressionProtein Cdc42Membrane proteinsTriple knockout miceEpsinDownstream regulationFoot process effacementPodocyte functionResponse factorPrimary podocytesCdc42Essential roleIndispensable roleProcess effacementExpressionRegulationKnockout miceIntegral rolePodocytesHomologCell adhesion molecule IGPR-1 activates AMPK connecting cell adhesion to autophagy
Amraei R, Alwani T, Ho R, Aryan Z, Wang S, Rahimi N. Cell adhesion molecule IGPR-1 activates AMPK connecting cell adhesion to autophagy. Journal Of Biological Chemistry 2020, 295: 16691-16699. PMID: 32978258, PMCID: PMC7864065, DOI: 10.1074/jbc.ra120.014790.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAMP-Activated Protein KinasesAnimalsAutophagyAutophagy-Related Protein-1 HomologBeclin-1CD28 AntigensCell AdhesionHEK293 CellsHumansI-kappa B KinaseIntracellular Signaling Peptides and ProteinsLipopolysaccharidesMicroscopy, FluorescenceMicrotubule-Associated ProteinsPhosphorylationPrimatesRNA, Guide, KinetoplastidaSirolimusSubstrate SpecificityConceptsIGPR-1Cell adhesionCell adhesion molecule IGPR-1Proline-rich receptor-1Serine/threonine kinaseKey serine/threonine kinaseAmino acid starvationBeclin-1Phosphorylation of AMPThreonine kinaseAutophagy stimuliKinase assaysLC3-II levelsCellular stressNutrient deprivationProtein kinaseCell adhesion moleculeProtein ULK1IκB kinase βEndothelial barrier functionKinase βCellular assaysPhosphorylationSubsequent activationCell detachmentIntegrin α6 mediates the drug resistance of acute lymphoblastic B-cell leukemia
Gang EJ, Kim HN, Hsieh YT, Ruan Y, Ogana HA, Lee S, Pham J, Geng H, Park E, Klemm L, Willman CL, Carroll WL, Mittelman SD, Orgel E, Oberley MJ, Parekh C, Abdel-Azim H, Bhojwani D, Wayne AS, De Arcangelis A, Georges-Labouesse E, Wayner E, Bonig H, Minasyan A, ten Hoeve J, Graeber TG, Müschen M, Heisterkamp N, Kim YM. Integrin α6 mediates the drug resistance of acute lymphoblastic B-cell leukemia. Blood 2020, 136: 210-223. PMID: 32219444, PMCID: PMC7357190, DOI: 10.1182/blood.2019001417.Peer-Reviewed Original ResearchConceptsAcute lymphoblastic leukemiaDrug resistanceTyrosine kinase inhibitor treatmentIntegrin α6Minimal residual diseaseProteomic analysisAcute lymphoblastic B-cell leukemiaAdhesion-mediated drug resistanceKinase inhibitor treatmentNovel therapeutic targetConditional knockout modelCentral nervous systemSrc signalingB-cell leukemiaPhosphorylated LynCell adhesionVivo deletionKnockout modelsResidual diseaseLymphoblastic leukemiaKinase inhibitionTherapeutic targetNervous systemB cellsBCR-ABL1Integrin-mediated adhesions in regulation of cellular senescence
Shin EY, Park JH, You ST, Lee CS, Won SY, Park JJ, Kim HB, Shim J, Soung NK, Lee OJ, Schwartz MA, Kim EG. Integrin-mediated adhesions in regulation of cellular senescence. Science Advances 2020, 6: eaay3909. PMID: 32494696, PMCID: PMC7202880, DOI: 10.1126/sciadv.aay3909.Peer-Reviewed Original ResearchConceptsClathrin-mediated endocytosisCellular senescenceG protein-coupled receptor kinasesProtein-coupled receptor kinasesElevated reactive oxygen species (ROS) productionIntegrin-mediated adhesionIntegrin endocytosisAmphiphysin 1Exchange factorReactive oxygen species productionReceptor kinaseOxygen species productionMolecular mechanismsCalpain cleavageSenescenceCell adhesionDirect competitionHuman fibroblastsGIT levelsSpecies productionΒPixNew therapeutic directionIntegrinsEndocytosisCentral role
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