2024
Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions
Tanaka K, Chen M, Prendergast A, Zhuang Z, Nasiri A, Joshi D, Hintzen J, Chung M, Kumar A, Mani A, Koleske A, Crawford J, Nicoli S, Schwartz M. Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions. The EMBO Journal 2024, 43: 3175-3191. PMID: 38886581, PMCID: PMC11294477, DOI: 10.1038/s44318-024-00142-0.Peer-Reviewed Original ResearchLatrophilin-2Affinity purification methodCell-cell junctionsHuman genetic dataPECAM-1SiRNA screenGenetic dataEndothelial cell response to fluid shear stressGA proteinsDownstream eventsEndothelial-specific knockoutG-proteinActivity assayShear stress mechanotransductionPlexin-D1Endothelial signalingJunctional complexesPurification methodVE-cadherinResponse to fluid shear stressVascular developmentGA residuesEndothelial junctionsGPCRsVEGF receptorsImpact of Abl2/Arg deficiency on anxiety and depressive behaviors in mice
Yao X, Chen R, Chen H, Koleske A, Xiao X. Impact of Abl2/Arg deficiency on anxiety and depressive behaviors in mice. Behavioural Brain Research 2024, 468: 115022. PMID: 38697301, DOI: 10.1016/j.bbr.2024.115022.Peer-Reviewed Original ResearchDepressive-like behaviorBehavioral testsMarble-burying behavior testAnxiety/depression-related behaviorsAnxiety-like behaviorElevated plus mazeTail suspension testEmotion-related behaviorsOpen field testWT micePlus mazeDepressive behaviorSuspension testAgonist gaboxadolMemory deficitsY-mazeAnxietyInhibitory neurotransmissionCompared to WT miceSensory/motor functionTissue injury responsesWild-typeHippocampusGABAergic synapseIntraperitoneal treatment
2023
Inhibition of Abelson Tyrosine-Protein Kinase 2 Suppresses the Development of Alcohol-Associated Liver Disease by Decreasing PPARgamma Expression
Malnassy G, Keating C, Gad S, Bridgeman B, Perera A, Hou W, Cotler S, Ding X, Choudhry M, Sun Z, Koleske A, Qiu W. Inhibition of Abelson Tyrosine-Protein Kinase 2 Suppresses the Development of Alcohol-Associated Liver Disease by Decreasing PPARgamma Expression. Cellular And Molecular Gastroenterology And Hepatology 2023, 16: 685-709. PMID: 37460041, PMCID: PMC10520367, DOI: 10.1016/j.jcmgh.2023.07.006.Peer-Reviewed Original ResearchConceptsAlcohol-fed miceLiver diseaseALD pathogenesisPPARγ expressionLiver injuryAlcohol feedingKnockout miceAlcohol-associated liver diseaseLiver tissueC57BL6/J miceAlcohol-induced accumulationAlcohol-induced steatosisOil Red O stainingWild-type miceHypoxia inducible factor 1 subunit alphaTreatment of ALDPPARγ protein expressionRed O stainingLiver-specific knockoutSubsequent lipid accumulationSubsequent RNA sequencingPotential molecular targetsAbl kinase inhibitorsQuantitative polymerase chain reactionLipid droplet formationCorrection: Trio family proteins as regulators of cell migration and morphogenesis in development and disease – mechanisms and cellular contexts
Bircher J, Koleske A. Correction: Trio family proteins as regulators of cell migration and morphogenesis in development and disease – mechanisms and cellular contexts. Journal Of Cell Science 2023, 136 PMID: 36763488, PMCID: PMC11034500, DOI: 10.1242/jcs.260984.Peer-Reviewed Original ResearchAbl2 mediates microtubule nucleation and repair via tubulin co-condensation
Duan D, Lyu W, Wu K, Wu C, Xiong Y, Koleske A. Abl2 mediates microtubule nucleation and repair via tubulin co-condensation. Biophysical Journal 2023, 122: 124a. DOI: 10.1016/j.bpj.2022.11.839.Peer-Reviewed Original Research
2022
Atypical nuclear envelope condensates linked to neurological disorders reveal nucleoporin-directed chaperone activities
Prophet SM, Rampello AJ, Niescier RF, Gentile JE, Mallik S, Koleske AJ, Schlieker C. Atypical nuclear envelope condensates linked to neurological disorders reveal nucleoporin-directed chaperone activities. Nature Cell Biology 2022, 24: 1630-1641. PMID: 36302970, PMCID: PMC10041656, DOI: 10.1038/s41556-022-01001-y.Peer-Reviewed Original ResearchAutoinhibition of the GEF activity of cytoskeletal regulatory protein Trio is disrupted in neurodevelopmental disorder-related genetic variants
Bircher JE, Corcoran EE, Lam TT, Trnka MJ, Koleske AJ. Autoinhibition of the GEF activity of cytoskeletal regulatory protein Trio is disrupted in neurodevelopmental disorder-related genetic variants. Journal Of Biological Chemistry 2022, 298: 102361. PMID: 35963430, PMCID: PMC9467883, DOI: 10.1016/j.jbc.2022.102361.Peer-Reviewed Original ResearchConceptsSpectrin repeatsGEF1 domainPleckstrin homology regionExchange factor domainKey regulatory mechanismCytoskeletal regulatory proteinsSmall GTPase Rac1Autoinhibitory constraintsAccessory domainsNeurodevelopmental disordersGEF activityMultiple neurodevelopmental disordersKinase domainHomology regionProtein TrioGTPase Rac1Regulatory proteinsRegulatory mechanismsFactor domainSRS-6Genetic variantsGef1Disease variantsEnzymatic activityBio-Layer InterferometryControl of Synapse Structure and Function by Actin and Its Regulators
Gentile JE, Carrizales MG, Koleske AJ. Control of Synapse Structure and Function by Actin and Its Regulators. Cells 2022, 11: 603. PMID: 35203254, PMCID: PMC8869895, DOI: 10.3390/cells11040603.Peer-Reviewed Original ResearchConceptsActin poolsOrganization of proteinsSynaptic actinOrganization of actinDisease risk genesKey neuronal functionsPost-synaptic compartmentsActin regulatorsDynamic regulationActin filamentsWhole-exome sequencingRisk genesIon channelsGenetic variantsActinRegulatorNeuronal functionSynapse structureExome sequencingPostsynaptic dendritic spinesKey functionsSpecialized junctionsGenesPresynaptic axon terminalsAxon terminals
2021
In vitro fluorescence assay to measure GDP/GTP exchange of guanine nucleotide exchange factors of Rho family GTPases
Blaise AM, Corcoran EE, Wattenberg ES, Zhang YL, Cottrell JR, Koleske AJ. In vitro fluorescence assay to measure GDP/GTP exchange of guanine nucleotide exchange factors of Rho family GTPases. Biology Methods And Protocols 2021, 7: bpab024. PMID: 35087952, PMCID: PMC8789339, DOI: 10.1093/biomethods/bpab024.Peer-Reviewed Original ResearchNucleotide exchange factorsGEF domainExchange factorGuanine nucleotide exchange factorsGDP/GTP exchangeRho family GEFsActivation of GTPasesFluorescence-based analysisRare variantsGTP loadingGTP exchangeRho familyHigh-throughput screeningWhole-exome sequencingCellular activitiesGenetic variantsGTPasesGEFExome sequencingCritical roleUser-friendly protocolComplete understandingHuman developmentVariantsGEFsMeasuring Cell-Edge Protrusion Dynamics during Spreading using Live-Cell Microscopy.
Lukic N, Saha T, Lapetina S, Gendler M, Lehmann G, Koleske AJ, Gil-Henn H. Measuring Cell-Edge Protrusion Dynamics during Spreading using Live-Cell Microscopy. Journal Of Visualized Experiments 2021 PMID: 34779432, PMCID: PMC8672187, DOI: 10.3791/63157.Peer-Reviewed Original ResearchConceptsCell edge protrusionCell migrationProtrusion dynamicsKey actin regulatorsLive-cell microscopyMulticellular organismsActin regulatorsCoordinated regulationEmbryonic developmentMembrane dynamicsEssential eventRegeneration of tissuesCancer metastasisTissue invasionPathological disordersRufflesProtrusionMigrationOrganismsRegulatorHomeostasisRegulationInvasionDysregulationDynamicsMeasuring Cell-Edge Protrusion Dynamics during Spreading using Live-Cell Microscopy
Lukic N, Saha T, Lapetina S, Gendler M, Lehmann G, Koleske A, Gil-Henn H. Measuring Cell-Edge Protrusion Dynamics during Spreading using Live-Cell Microscopy. Journal Of Visualized Experiments 2021 DOI: 10.3791/63157-v.Peer-Reviewed Original ResearchRegulation of the NMDA receptor by its cytoplasmic domains: (How) is the tail wagging the dog?
Ishchenko Y, Carrizales MG, Koleske AJ. Regulation of the NMDA receptor by its cytoplasmic domains: (How) is the tail wagging the dog? Neuropharmacology 2021, 195: 108634. PMID: 34097949, PMCID: PMC8410658, DOI: 10.1016/j.neuropharm.2021.108634.Peer-Reviewed Original ResearchConceptsCarboxyl-terminal domainN-methyl-D-aspartate receptorsUnique modular architectureIntracellular C-tailAmino acid sequenceDocking motifAttention deficit hyperactivity disorderKnown proteinsCytoplasmic domainC-tailTerminal domainSequence homologyAcid sequenceSynapse developmentSynaptic targetingCovalent modificationGenetic variantsGlutamate receptor subunitsAllosteric modulationImportant functionsReceptor subunitsIntellectual disabilityMetabotropic signalingSubunitsProteinPlatelet-derived growth factor receptor beta activates Abl2 via direct binding and phosphorylation
Wu K, Wu H, Lyu W, Kim Y, Furdui CM, Anderson KS, Koleske AJ. Platelet-derived growth factor receptor beta activates Abl2 via direct binding and phosphorylation. Journal Of Biological Chemistry 2021, 297: 100883. PMID: 34144039, PMCID: PMC8259415, DOI: 10.1016/j.jbc.2021.100883.Peer-Reviewed Original ResearchConceptsAbl family kinasesFamily kinasesPlatelet-derived growth factor receptor betaGrowth factor receptor betaAbl familySrc homology 2 domainSrc homology 3 domainDiverse cellular stimuliPost-translational modificationsN-terminal halfNonreceptor tyrosine kinaseMultiple novel sitesAutoinhibited conformationSrc homologyCytoskeleton organizationCytoplasmic domainCellular stimuliKinase domainGrowth factor receptorReceptor betaKinase activityMolecular mechanismsTyrosine kinaseDirect bindingKinaseWhat is the role of synaptic protein TRIO's spectrin repeats?
Corcoran E, Bircher J, Koleske A. What is the role of synaptic protein TRIO's spectrin repeats? The FASEB Journal 2021, 35 DOI: 10.1096/fasebj.2021.35.s1.01837.Peer-Reviewed Original ResearchSpectrin repeatsProper neuronal developmentSpectrin repeat domainRare damaging variantsDisease-associated mutationsAccessory domainsCatalytic domainRepeat domainRegulatory proteinsRepeat functionDe novo missense mutationsSignaling mechanismDamaging mutationsNeuronal developmentDamaging variantsDisease mutationsBiochemical eventsNovo missense mutationNeurodevelopmental disordersMissense mutationsSpectrinRepeatsMutationsDomainTherapeutic strategiesAbl2:Cortactin Interactions Regulate Dendritic Spine Stability via Control of a Stable Filamentous Actin Pool
Shaw JE, Kilander MBC, Lin YC, Koleske AJ. Abl2:Cortactin Interactions Regulate Dendritic Spine Stability via Control of a Stable Filamentous Actin Pool. Journal Of Neuroscience 2021, 41: 3068-3081. PMID: 33622779, PMCID: PMC8026353, DOI: 10.1523/jneurosci.2472-20.2021.Peer-Reviewed Original ResearchConceptsDendritic spine stabilityDendritic spinesSpine stabilityTonic increaseSubset of spinesSexes of miceMost excitatory synapsesCortactin interactionsGluN2B levelsSpine densitySpine lossArg nonreceptor tyrosine kinaseKinetically distinct poolsExcitatory synapsesHippocampal neuronsSynaptic activitySpine enlargementSpineSpine sizeSpine actinActivity-dependent spine enlargementSpine shapeStructural plasticityDistinct poolsTyrosine kinaseTrio family proteins as regulators of cell migration and morphogenesis in development and disease – mechanisms and cellular contexts
Bircher JE, Koleske AJ. Trio family proteins as regulators of cell migration and morphogenesis in development and disease – mechanisms and cellular contexts. Journal Of Cell Science 2021, 134: jcs248393. PMID: 33568469, PMCID: PMC7888718, DOI: 10.1242/jcs.248393.Peer-Reviewed Original ResearchConceptsFamily proteinsCellular contextProtein-protein interaction domainsHuman diseasesProtein trafficking pathwaysLarge multidomain proteinCell surface receptorsTrio proteinsUNC-73Cell morphogenesisProtein traffickingTrafficking pathwaysMultidomain proteinsInteraction domainInteraction partnersKey regulatorBiological contextTissue organizationCell migrationSurface receptorsProteinTrio familiesRecent discoveryMorphogenesisRegulator
2020
Crystal structure of a guanine nucleotide exchange factor encoded by the scrub typhus pathogen Orientia tsutsugamushi
Lim C, Berk JM, Blaise A, Bircher J, Koleske AJ, Hochstrasser M, Xiong Y. Crystal structure of a guanine nucleotide exchange factor encoded by the scrub typhus pathogen Orientia tsutsugamushi. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 30380-30390. PMID: 33184172, PMCID: PMC7720168, DOI: 10.1073/pnas.2018163117.Peer-Reviewed Original ResearchConceptsBacterial GEFStructure-guided mutational analysisExchange factor domainRho family GTPasesObvious sequence similarityRho GTPases Rac1Pathogen Orientia tsutsugamushiAlters cell morphologyInteraction screenConvergent evolutionGEF domainHost interactorsExchange factorNucleotide displacementGEF activityCellular processesSequence similarityCytoskeletal structuresGTPases Rac1Ectopic expressionMutational analysisGEFRac1Factor domainPathogenic bacteriumTwo-color nanoscopy of organelles for extended times with HIDE probes
Chu L, Tyson J, Shaw JE, Rivera-Molina F, Koleske AJ, Schepartz A, Toomre DK. Two-color nanoscopy of organelles for extended times with HIDE probes. Nature Communications 2020, 11: 4271. PMID: 32848153, PMCID: PMC7450044, DOI: 10.1038/s41467-020-17859-1.Peer-Reviewed Original ResearchNeural Stem Cells Direct Axon Guidance via Their Radial Fiber Scaffold
Kaur N, Han W, Li Z, Madrigal MP, Shim S, Pochareddy S, Gulden FO, Li M, Xu X, Xing X, Takeo Y, Li Z, Lu K, Imamura Kawasawa Y, Ballester-Lurbe B, Moreno-Bravo JA, Chédotal A, Terrado J, Pérez-Roger I, Koleske AJ, Sestan N. Neural Stem Cells Direct Axon Guidance via Their Radial Fiber Scaffold. Neuron 2020, 107: 1197-1211.e9. PMID: 32707082, PMCID: PMC7529949, DOI: 10.1016/j.neuron.2020.06.035.Peer-Reviewed Original ResearchConceptsNeural stem cellsDendritic spine formationNeural circuit formationRadial glia-like neural stem cellsMedial ganglionic eminenceRadial fibersAxon guidanceStem cellsCorticospinal neuronsGlobus pallidusMacroglial cellsGanglionic eminenceCircuit formationVentricular zoneSpine formationRnd3/RhoENeuronsMidline crossingExpression of Rnd3Rho GTPaseCellsExpressionUnexpected roleAtypical Rho GTPaseRnd3ABL1, Overexpressed in Hepatocellular Carcinomas, Regulates Expression of NOTCH1 and Promotes Development of Liver Tumors in Mice
Wang F, Hou W, Chitsike L, Xu Y, Bettler C, Perera A, Bank T, Cotler SJ, Dhanarajan A, Denning MF, Ding X, Breslin P, Qiang W, Li J, Koleske AJ, Qiu W. ABL1, Overexpressed in Hepatocellular Carcinomas, Regulates Expression of NOTCH1 and Promotes Development of Liver Tumors in Mice. Gastroenterology 2020, 159: 289-305.e16. PMID: 32171747, PMCID: PMC7387191, DOI: 10.1053/j.gastro.2020.03.013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, HepatocellularCell Line, TumorDatasets as TopicDisease Models, AnimalFemaleGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansKaplan-Meier EstimateLiverLiver NeoplasmsMaleMicePhosphorylationPrognosisProto-Oncogene MasProto-Oncogene Proteins c-ablProto-Oncogene Proteins c-mycPyrimidinesReceptor, Notch1Xenograft Model Antitumor AssaysConceptsShorter survival timeLiver tumorsExpression of Notch1Hepatocellular carcinomaHuman HCC cellsHCC cellsXenograft tumorsSurvival timeExpression of MYCLiver tissueTreatment of HCCAlbumin-Cre miceNon-tumor liver tissuesABL proto-oncogene 1Nontumor liver tissuesHuman HCC specimensHuh7 HCC cellsHepatocyte-specific disruptionHCC tissue microarrayProto-oncogene 1HCC cell linesShort hairpin RNACancer Genome AtlasKnockdown of Notch1Tumor levels