2022
Control 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
Measuring 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 disordersRufflesProtrusionMigrationOrganismsRegulatorHomeostasisRegulationInvasionDysregulationDynamicsAbl2: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 kinase
2020
Functional interactions of ion channels with the actin cytoskeleton: does coupling to dynamic actin regulate NMDA receptors?
Shaw JE, Koleske AJ. Functional interactions of ion channels with the actin cytoskeleton: does coupling to dynamic actin regulate NMDA receptors? The Journal Of Physiology 2020, 599: 431-441. PMID: 32034761, PMCID: PMC7416480, DOI: 10.1113/jp278702.Peer-Reviewed Original ResearchConceptsActin cytoskeletonIon channelsPostsynaptic compartmentsCytoskeletal protein actinActin binding proteinsNeurotransmitter release machineryNeurotransmitter receptorsProtein actinSynaptic neurotransmitter receptorsΑ-actininMolecular mechanismsBinding proteinCytoskeletonMolecular linkageFunctional interactionRelease machineryDiverse collectionActinNMDA receptorsTraffickingChannel openingProteinVoltage-gated NaReceptorsCompartments
2018
Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension
Zhang K, Lyu W, Yu J, Koleske AJ. Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension. Molecular Biology Of The Cell 2018, 29: 2863-2873. PMID: 30256707, PMCID: PMC6249870, DOI: 10.1091/mbc.e18-01-0044.Peer-Reviewed Original ResearchConceptsCytoskeletal interactionsLamellipodium extensionTotal internal reflection fluorescence microscopyActin-rich structuresActin wavesActin-rich protrusionsN-terminal halfC-terminal halfNonreceptor tyrosine kinaseReflection fluorescence microscopyFoci colocalizeComplementation analysisLamellipodia protrusionKnockout cellsLamellipodium tipActin filament stabilizerCell shapeBind actinTyrosine kinaseCortactinABL2Fluorescence microscopyIntegrin β3High spatiotemporal resolutionPaxillinCortactin stabilization of actin requires actin-binding repeats and linker, is disrupted by specific substitutions, and is independent of nucleotide state
Scherer AN, Anand NS, Koleske AJ. Cortactin stabilization of actin requires actin-binding repeats and linker, is disrupted by specific substitutions, and is independent of nucleotide state. Journal Of Biological Chemistry 2018, 293: 13022-13032. PMID: 29929984, PMCID: PMC6109930, DOI: 10.1074/jbc.ra118.004068.Peer-Reviewed Original ResearchConceptsHematopoietic cell-specific Lyn substrate 1Nucleotide stateActin bindingActin filamentsTotal internal reflection fluorescence microscopyActin-binding proteins cortactinActin cosedimentation assaysActin-rich structuresHigh-affinity actin bindingADP-actin filamentsReflection fluorescence microscopyAdjacent linker regionActin filament bindingArp2/3 complexCortactin repeatsCellular functionsActin stabilityCosedimentation assaysActin stabilizationProtein cortactinLamellipodial protrusionGTPase regulatorFilament depolymerizationLinker regionActin depolymerization
2017
Phosphorylated cortactin recruits Vav2 guanine nucleotide exchange factor to activate Rac3 and promote invadopodial function in invasive breast cancer cells
Rosenberg BJ, Gil-Henn H, Mader CC, Halo T, Yin T, Condeelis J, Machida K, Wu YI, Koleske AJ. Phosphorylated cortactin recruits Vav2 guanine nucleotide exchange factor to activate Rac3 and promote invadopodial function in invasive breast cancer cells. Molecular Biology Of The Cell 2017, 28: 1347-1360. PMID: 28356423, PMCID: PMC5426849, DOI: 10.1091/mbc.e16-12-0885.Peer-Reviewed Original ResearchConceptsInvasive breast cancer cellsInvadopodium maturationBreast cancer cellsActin nucleation-promoting factorCancer cellsSH2 domain bindsHuman SH2 domainsMatrix degradationNucleation-promoting factorsGuanine nucleotide exchange factor Vav2Actin-rich protrusionsSubsequent cell invasionExchange factor Vav2Active Rac3Invasive MDA-MB-231 breast cancer cellsMDA-MB-231 breast cancer cellsInvadopodial functionSH2 domainDomain bindsExchange factorKinase cascadeCortactin phosphorylationActin polymerizationMutant formsInvadopodia
2014
Abl2/Abl-related Gene Stabilizes Actin Filaments, Stimulates Actin Branching by Actin-related Protein 2/3 Complex, and Promotes Actin Filament Severing by Cofilin*
Courtemanche N, Gifford SM, Simpson MA, Pollard TD, Koleske AJ. Abl2/Abl-related Gene Stabilizes Actin Filaments, Stimulates Actin Branching by Actin-related Protein 2/3 Complex, and Promotes Actin Filament Severing by Cofilin*. Journal Of Biological Chemistry 2014, 290: 4038-4046. PMID: 25540195, PMCID: PMC4326814, DOI: 10.1074/jbc.m114.608117.Peer-Reviewed Original ResearchAbelson phosphorylation of CLASP2 modulates its association with microtubules and actin
Engel U, Zhan Y, Long JB, Boyle SN, Ballif BA, Dorey K, Gygi SP, Koleske AJ, VanVactor D. Abelson phosphorylation of CLASP2 modulates its association with microtubules and actin. Cytoskeleton 2014, 71: 195-209. PMID: 24520051, PMCID: PMC4054870, DOI: 10.1002/cm.21164.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActinsAmino Acid SequenceAnimalsCell AdhesionChlorocebus aethiopsCOS CellsGrowth ConesHEK293 CellsHumansMicrotubule-Associated ProteinsMicrotubulesMolecular Sequence DataPhosphorylationPhosphotyrosinePlatelet-Derived Growth FactorProtein BindingProto-Oncogene Proteins c-ablSignal TransductionSubcellular FractionsSubstrate SpecificityXenopusConceptsAbelson non-receptor tyrosine kinasesNon-receptor tyrosine kinaseBona fide substrateF-actin structuresVertebrate cellsFide substrateProtein CLASPInteraction domainPDGF stimulationCLASP2Tyrosine residuesF-actinTyrosine kinaseNeural developmentAbl phosphorylationMicrotubulesPhosphorylationGrowth conesCytoskeletonABLFunctional relationshipDrosophilaMultiple stagesKinaseNeurulation
2013
β1 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
Arg/Abl2 Modulates the Affinity and Stoichiometry of Binding of Cortactin to F‑Actin
MacGrath SM, Koleske AJ. Arg/Abl2 Modulates the Affinity and Stoichiometry of Binding of Cortactin to F‑Actin. Biochemistry 2012, 51: 6644-6653. PMID: 22849492, PMCID: PMC3556572, DOI: 10.1021/bi300722t.Peer-Reviewed Original ResearchConceptsStoichiometry of bindingF-actinTerminal calponin homology domainRecruitment of cortactinActin cosedimentation assaysArp2/3 complex activatorsCell edge protrusionActin network assemblyCalponin homology domainProtein-protein interactionsCortactin bindsHomology domainActin cytoskeletonArg CDeletion mutantsCosedimentation assaysFilamentous actinEdge protrusionComplex activatorActin binding propertiesCortactinActin filamentsNetwork assemblyDownstream effectsBinding
2010
Specific tyrosine phosphorylation sites on cortactin regulate Nck1-dependent actin polymerization in invadopodia
Oser M, Mader CC, Gil-Henn H, Magalhaes M, Bravo-Cordero JJ, Koleske AJ, Condeelis J. Specific tyrosine phosphorylation sites on cortactin regulate Nck1-dependent actin polymerization in invadopodia. Journal Of Cell Science 2010, 123: 3662-3673. PMID: 20971703, PMCID: PMC3037016, DOI: 10.1242/jcs.068163.Peer-Reviewed Original ResearchConceptsTyrosine phosphorylation sitesTumor cell invasionActin polymerizationPhosphorylation sitesCell invasionTyrosine 421Actin barbed endsPhosphorylation of tyrosineRegulatory switchSH2 domainMembrane protrusionsInvadopodiaCrucial residuesCortactinBarbed endsDirect bindingInvasive carcinoma cellsPhosphorylationNck1Carcinoma cellsFRET interactionsInvasionCellsPhosphotyrosineSitesRegulation of Actin Polymerization and Adhesion-Dependent Cell Edge Protrusion by the Abl-Related Gene (Arg) Tyrosine Kinase and N-WASp
Miller MM, Lapetina S, MacGrath SM, Sfakianos MK, Pollard TD, Koleske AJ. Regulation of Actin Polymerization and Adhesion-Dependent Cell Edge Protrusion by the Abl-Related Gene (Arg) Tyrosine Kinase and N-WASp. Biochemistry 2010, 49: 2227-2234. PMID: 20146487, PMCID: PMC2836179, DOI: 10.1021/bi901721u.Peer-Reviewed Original ResearchConceptsCell edge protrusionN-WASPActin polymerizationEdge protrusionN-WASP-dependent actin polymerizationGene Tyrosine KinaseFluorescent protein fusionsNovel binding partnerExtracellular cuesProtein fusionsSH2 domainExtracellular stimuliActin cytoskeletonSH3 domainBinding partnerCellular protrusionsPoint mutantsAffinity purificationTyrosine kinasePhysical interactionSH3PhosphorylationArgABLPotential link
2009
Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation
Oser M, Yamaguchi H, Mader CC, Bravo-Cordero JJ, Arias M, Chen X, DesMarais V, van Rheenen J, Koleske AJ, Condeelis J. Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation. Journal Of Cell Biology 2009, 186: 571-587. PMID: 19704022, PMCID: PMC2733743, DOI: 10.1083/jcb.200812176.Peer-Reviewed Original ResearchMeSH KeywordsActin Depolymerizing FactorsActin-Related Protein 2-3 ComplexActinsAdaptor Proteins, Signal TransducingAnimalsCell Line, TumorCortactinEpidermal Growth FactorExtracellular MatrixHumansMammary Neoplasms, AnimalMatrix Metalloproteinase 14Neoplasm InvasivenessOncogene Protein pp60(v-src)Oncogene ProteinsPhosphorylationProtein Structure, TertiaryRatsRecombinant Fusion ProteinsRNA, Small InterferingTyrosineWiskott-Aldrich Syndrome Protein, NeuronalConceptsInvadopodium assemblyActin polymerizationCortactin phosphorylationArp2/3 complex-dependent actin polymerizationArp2/3-dependent actin polymerizationComplex-dependent actin polymerizationBarbed end formationN-WASP activityCarcinoma cellsMembrane protrusionsEnd formationSevering activityInvadopodiaMaster switchActin filamentsBarbed endsCortactinInvasive carcinoma cellsMetastatic carcinoma cellsNovel mechanismPhosphorylationCofilinMatrix degradationMaturationAssemblyArg interacts with cortactin to promote adhesion-dependent cell edge protrusion
Lapetina S, Mader CC, Machida K, Mayer BJ, Koleske AJ. Arg interacts with cortactin to promote adhesion-dependent cell edge protrusion. Journal Of Cell Biology 2009, 185: 503-519. PMID: 19414610, PMCID: PMC2700396, DOI: 10.1083/jcb.200809085.Peer-Reviewed Original ResearchConceptsCell edge protrusionEdge protrusionActin polymerization machineryAdhesion-dependent phosphorylationCell-matrix adhesionPro-rich motifMutation of residuesPolymerization machinerySH2 domainDomain bindsC-terminusCortactinMolecular mechanismsGene kinaseSimilar defectsAdditional binding sitesCatalytic eventsBinding sitesArgInteractsFibroblast adhesionProtrusionNck1KinasePhosphorylation
2008
The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse
Huang Y, Comiskey EO, Dupree RS, Li S, Koleske AJ, Burkhardt JK. The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse. Blood 2008, 112: 111-119. PMID: 18305217, PMCID: PMC2435682, DOI: 10.1182/blood-2007-10-118232.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdaptor Proteins, Signal TransducingAnimalsCells, CulturedHumansInterleukin-2Jurkat CellsLymphocyte ActivationMiceMice, KnockoutPhosphorylationProtein BindingProteinsProto-Oncogene Proteins c-ablPseudopodiaReceptors, Antigen, T-CellSignal TransductionT-LymphocytesTranscription, GeneticWiskott-Aldrich Syndrome Protein FamilyConceptsC-AblImmune synapseActin responseC-Abl nonreceptor tyrosine kinaseT cell activationTyrosine kinaseC-Abl tyrosine kinaseC-Abl bindsActin regulatory proteinsNonreceptor tyrosine kinaseChemokine-induced T cell migrationT cell receptor engagementSH2 domainActin dynamicsActin reorganizationTyrosine phosphorylationRegulatory proteinsActin polymerizationDownstream eventsNormal localizationConditional knockout miceCoordinate actionReceptor engagementKinaseLamellipodial spreading
2007
A Critical Role for Cortactin Phosphorylation by Abl-Family Kinases in PDGF-Induced Dorsal-Wave Formation
Boyle SN, Michaud GA, Schweitzer B, Predki PF, Koleske AJ. A Critical Role for Cortactin Phosphorylation by Abl-Family Kinases in PDGF-Induced Dorsal-Wave Formation. Current Biology 2007, 17: 445-451. PMID: 17306540, DOI: 10.1016/j.cub.2007.01.057.Peer-Reviewed Original ResearchConceptsAbl family kinasesCortactin phosphorylationActin regulatory protein cortactinTyrosine kinaseAbl family tyrosine kinasesSrc family kinasesNonreceptor tyrosine kinaseHuman protein microarrayCell morphogenesisActin reorganizationCytoskeletal rearrangementsProtein cortactinGrowth factor receptorLamellipodial protrusionCytoskeletal structuresCell motilityProper regulationPDGF treatmentTyrosine residuesCortactinKinaseNovel substrateDownstream actionsPhosphorylationProtein microarrays
2005
Integrin-Mediated Dendrite Branch Maintenance Requires Abelson (Abl) Family Kinases
Moresco EM, Donaldson S, Williamson A, Koleske AJ. Integrin-Mediated Dendrite Branch Maintenance Requires Abelson (Abl) Family Kinases. Journal Of Neuroscience 2005, 25: 6105-6118. PMID: 15987940, PMCID: PMC6725048, DOI: 10.1523/jneurosci.1432-05.2005.Peer-Reviewed Original ResearchConceptsCortical dendritesPostnatal day 21Nervous system functionDendrite lossCortical neuronsSemaphorin 7ADay 21Arg kinase activityArbor sizeMouse brainArbor structureDendrite maintenanceEarly adulthoodNeurite branchingTyrosine kinaseNeurite branchesDendritesNonreceptor tyrosine kinaseIntegrin receptorsCritical determinantLaminin-1System functionKinase activityBranch dynamicsDendrite branches
2004
The Arg Non-receptor Tyrosine Kinase Modifies F-actin Structure
Galkin VE, Orlova A, Koleske AJ, Egelman EH. The Arg Non-receptor Tyrosine Kinase Modifies F-actin Structure. Journal Of Molecular Biology 2004, 346: 565-575. PMID: 15670605, DOI: 10.1016/j.jmb.2004.11.078.Peer-Reviewed Original ResearchConceptsSubdomain 1Domain bindsActin filamentsF-actinSingle particle image analysisActin-bundling activityNon-receptor tyrosine kinaseCalponin homology domainActin-binding domainF-actin structuresActin subdomain 1Homology domainAbl familyCH domainCell motilityAdjacent protomersTyrosine kinaseParticle image analysisActin protomersConformational changesCooperative bindingARG proteinProtomersArgProteinThe Abl-related gene (Arg) requires its F-actin–microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion
Miller AL, Wang Y, Mooseker MS, Koleske AJ. The Abl-related gene (Arg) requires its F-actin–microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion. Journal Of Cell Biology 2004, 165: 407-420. PMID: 15138293, PMCID: PMC2172189, DOI: 10.1083/jcb.200308055.Peer-Reviewed Original ResearchConceptsLamellipodial dynamicsCross-linking activityF-actin-binding domainFluorescent protein fusionsMT-binding domainNonreceptor tyrosine kinaseFilamentous actin bundlesWild-type fibroblastsCell polarityProtein fusionsMembrane protrusionsCell peripheryLamellipodial protrusionCell protrusionsActin bundlesMolecular mechanismsTyrosine kinaseF-actinMicrotubulesArgFibroblast adhesionABLHigh affinityFibroblastsProtrusion