Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice
Ishchenko Y, Jeng A, Feng S, Nottoli T, Manriquez-Rodriguez C, Nguyen K, Carrizales M, Vitarelli M, Corcoran E, Greer C, Myers S, Koleske A. Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice. ELife 2025, 13: rp103620. PMID: 40488445, PMCID: PMC12148328, DOI: 10.7554/elife.103620.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderGuanine nucleotide exchange factorNeurodevelopmental disordersPresynaptic glutamate releaseLayer 5 pyramidal neuronsAssociated with neurodevelopmental disordersIntellectual disabilitySpectrum disorderMouse behaviorCognitive behaviorNucleotide exchange factorNeuronal developmentBrain developmentGlutamate releaseIncreased Rac1 activityBrain sizeSynaptic functionControlling neuronal developmentSchizophreniaImpaired abilityAssociated with increased levelsNeurodevelopmental eventsActive GTPaseGEF Tiam1Exchange factorHeterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice
Ishchenko Y, Jeng A, Feng S, Nottoli T, Manriquez-Rodriguez C, Nguyen K, Carrizales M, Vitarelli M, Corcoran E, Greer C, Myers S, Koleske A. Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice. ELife 2025, 13 DOI: 10.7554/elife.103620.3.Peer-Reviewed Original ResearchAutism spectrum disorderGuanine nucleotide exchange factorNeurodevelopmental disordersPresynaptic glutamate releaseLayer 5 pyramidal neuronsAssociated with neurodevelopmental disordersIntellectual disabilitySpectrum disorderMouse behaviorCognitive behaviorNucleotide exchange factorSchizophreniaNeuronal developmentBrain developmentGlutamate releaseIncreased Rac1 activityBrain sizeSynaptic functionControlling neuronal developmentImpaired abilityAssociated with increased levelsNeurodevelopmental eventsActive GTPaseGEF Tiam1Exchange factorActivation of a Potassium Channel Mutation That Causes Spinocerebellar Ataxia Promotes Aggregation of the RhoGEF Domain‐Containing Protein Plekhg4
Zhang Y, Andrawis A, Kaczmarek L. Activation of a Potassium Channel Mutation That Causes Spinocerebellar Ataxia Promotes Aggregation of the RhoGEF Domain‐Containing Protein Plekhg4. The FASEB Journal 2025, 39: e70552. PMID: 40249242, DOI: 10.1096/fj.202402809rr.Peer-Reviewed Original ResearchConceptsGuanine nucleotide exchange factorKv3.3 channelsNucleation of actin filamentsPlasma membraneNucleotide exchange factorPurkinje neuronsRegulating Rac1 activitySpinocerebellar ataxiaPotassium channel mutationsAuditory brainstem neuronsCerebellar Purkinje neuronsActin nucleationPurkinje cell activityWild-type channelsExchange factorActin filamentsPotential new therapeutic approachCytoplasmic proteinsTreatment of spinocerebellar ataxiaRac1 activationHAX-1Cytoplasmic aggregatesRegulate excitabilityBrainstem neuronsCHO cells
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