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 ResearchMeSH KeywordsCytoskeletal ProteinsCytoskeletonGuanineHumansMonomeric GTP-Binding ProteinsNeurodevelopmental DisordersSpectrinConceptsSpectrin 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 Interferometry
2019
Trio Haploinsufficiency Causes Neurodevelopmental Disease-Associated Deficits
Katrancha SM, Shaw JE, Zhao AY, Myers SA, Cocco AR, Jeng AT, Zhu M, Pittenger C, Greer CA, Carr SA, Xiao X, Koleske AJ. Trio Haploinsufficiency Causes Neurodevelopmental Disease-Associated Deficits. Cell Reports 2019, 26: 2805-2817.e9. PMID: 30840899, PMCID: PMC6436967, DOI: 10.1016/j.celrep.2019.02.022.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGuanine Nucleotide Exchange FactorsHumansMaleMiceMice, KnockoutNeurodevelopmental DisordersNeuronsProtein Serine-Threonine KinasesSynapsesConceptsHeterozygous coding mutationsDendritic spine densityHippocampus of miceNeurodevelopmental disordersLong-term potentiationDendritic spine defectsPostsynaptic deficitsSpine densityCortical synapsesDendritic arborizationExcitatory neuronsMotor coordinationHaploinsufficient miceKnockout miceTherapeutic interventionsBipolar disorderProtein kinase A (PKA) signalingNeuronal structuresSpine defectsIncreases anxietyMiceDisordersDeficitsCoding mutationsA Signaling
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