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 bacteriumNeural 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 GTPaseRnd3
2017
Neurodevelopmental disease-associated de novo mutations and rare sequence variants affect TRIO GDP/GTP exchange factor activity
Katrancha SM, Wu Y, Zhu M, Eipper BA, Koleske AJ, Mains RE. Neurodevelopmental disease-associated de novo mutations and rare sequence variants affect TRIO GDP/GTP exchange factor activity. Human Molecular Genetics 2017, 26: 4728-4740. PMID: 28973398, PMCID: PMC5886096, DOI: 10.1093/hmg/ddx355.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsDatabases, Nucleic AcidGuanine Nucleotide Exchange FactorsGuanosine DiphosphateGuanosine TriphosphateHEK293 CellsHumansMiceMice, KnockoutMutationNeurodevelopmental DisordersProtein DomainsProtein Serine-Threonine KinasesRac1 GTP-Binding ProteinRho GTP-Binding ProteinsRhoA GTP-Binding ProteinConceptsDe novo mutationsNeurodevelopmental disordersRare sequence variantsTriple functional domain proteinNovo mutationsComplex neurodevelopmental disorderBipolar disorderTherapeutic progressSequence variantsImpaired inhibitionProtein levelsDisordersMolecular pathwaysMillions of peopleIntellectual disabilityRare variantsNeurite outgrowthGenetic damageFactor activityMutationsExchange factor activityDistinct specificitiesPoor understandingRac1Activity
2013
Corticosteroid-Induced Neural Remodeling Predicts Behavioral Vulnerability and Resilience
Gourley SL, Swanson AM, Koleske AJ. Corticosteroid-Induced Neural Remodeling Predicts Behavioral Vulnerability and Resilience. Journal Of Neuroscience 2013, 33: 3107-3112. PMID: 23407965, PMCID: PMC3711631, DOI: 10.1523/jneurosci.2138-12.2013.Peer-Reviewed Original ResearchConceptsStressor exposureDendritic spinesDendritic spine densityRecovery periodCA1 pyramidal neuronsHippocampal CA1 neuronsCertain neuron populationsStress hormone exposureStress-related modificationsDistinct brain regionsBehavioral vulnerabilityDendritic retractionPyramidal neuronsCA1 neuronsNeural remodelingSpine densityStress-related diseasesHippocampal CA1Orbital cortexBasal amygdalaDendritic arborsHormone exposureNeuron populationsBrain regionsBrain circuits
2011
Invadopodia: RhoC Runs Rings around Cofilin
MacGrath SM, Koleske AJ. Invadopodia: RhoC Runs Rings around Cofilin. Current Biology 2011, 21: r280-r282. PMID: 21514509, PMCID: PMC3376399, DOI: 10.1016/j.cub.2011.03.035.Peer-Reviewed Original Research
2010
Increased Dendrite Branching in AβPP/PS1 Mice and Elongation of Dendrite Arbors by Fasudil Administration
Couch BA, DeMarco GJ, Gourley SL, Koleske AJ. Increased Dendrite Branching in AβPP/PS1 Mice and Elongation of Dendrite Arbors by Fasudil Administration. Journal Of Alzheimer's Disease 2010, 20: 1003-1008. PMID: 20413901, PMCID: PMC3077946, DOI: 10.3233/jad-2010-091114.Peer-Reviewed Original ResearchConceptsDendrite arborsPS1 miceAβPP/PS1 miceAmyloid-beta overproductionPS1 transgenic miceCA1 pyramidal neuronsROCK inhibitor fasudilROCK signalingPyramidal neuronsDendritic regressionFasudil administrationPharmacological reductionInhibitor fasudilTransgenic miceAlzheimer's diseaseMiceDendrite branchingRho-kinaseArborsDiseaseNeuronsSignalingAtrophyFasudilAbeta
2007
The Abl-related Gene Tyrosine Kinase Acts through p190RhoGAP to Inhibit Actomyosin Contractility and Regulate Focal Adhesion Dynamics upon Adhesion to Fibronectin
Peacock JG, Miller AL, Bradley WD, Rodriguez OC, Webb DJ, Koleske AJ. The Abl-related Gene Tyrosine Kinase Acts through p190RhoGAP to Inhibit Actomyosin Contractility and Regulate Focal Adhesion Dynamics upon Adhesion to Fibronectin. Molecular Biology Of The Cell 2007, 18: 3860-3872. PMID: 17652459, PMCID: PMC1995720, DOI: 10.1091/mbc.e07-01-0075.Peer-Reviewed Original ResearchConceptsFocal adhesion dynamicsFocal adhesionsActomyosin contractilityAdhesion dynamicsActin-dependent protrusionsGene Tyrosine KinaseCell migrationCell body translocationAbl family kinasesWild-type cellsC-terminal halfDistinct functional domainsN-terminal halfF-actin stress fibersStress fiber formationInhibits cell migrationKinase inhibitsFamily kinasesCell peripheryStress fibersActin polymerizationFunctional domainsKinase activityTyrosine kinaseWT cells
2006
Integrin Signaling through Arg Activates p190RhoGAP by Promoting Its Binding to p120RasGAP and Recruitment to the Membrane
Bradley WD, Hernández SE, Settleman J, Koleske AJ. Integrin Signaling through Arg Activates p190RhoGAP by Promoting Its Binding to p120RasGAP and Recruitment to the Membrane. Molecular Biology Of The Cell 2006, 17: 4827-4836. PMID: 16971514, PMCID: PMC1635390, DOI: 10.1091/mbc.e06-02-0132.Peer-Reviewed Original ResearchConceptsCell peripheryP120 bindingGene Tyrosine KinaseRho family GTPases RhoAActin stress fibersIntegrin-mediated adhesionWild-type fibroblastsP190 phosphorylationFocal adhesionsGTPases RhoARho activityStress fibersEssential effectorTyrosine kinaseAdhesive environmentCell attachmentP190P120P190RhoGAPP120RasGAPPhosphorylationComplex formationBindingRecruitmentRho