2022
Autoinhibition 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 developmentVariantsGEFsRegulation 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 signalingSubunitsProtein