2017
Synaptic NMDA Receptor Activation Induces Ubiquitination and Degradation of STEP61
Xu J, Kurup P, Nairn AC, Lombroso PJ. Synaptic NMDA Receptor Activation Induces Ubiquitination and Degradation of STEP61. Molecular Neurobiology 2017, 55: 3096-3111. PMID: 28466270, PMCID: PMC5668205, DOI: 10.1007/s12035-017-0555-x.Peer-Reviewed Original ResearchConceptsMK-801-treated miceProtein tyrosine Phosphatase 61GluN1/GluN2B receptorsNMDA receptor signalingD-serine treatmentMouse frontal cortexNMDAR signalingSynaptic NMDARsCortical samplesHuman schizophreniaTherapeutic effectFrontal cortexGluN2B receptorsSynaptic plasticityNeurological disordersCognitive deficitsReceptor signalingD-serineSTEP61SchizophreniaBicucullineMiceProteasomal degradationSurface localizationSignaling
2015
Inhibition of the tyrosine phosphatase STEP61 restores BDNF expression and reverses motor and cognitive deficits in phencyclidine-treated mice
Xu J, Kurup P, Baguley TD, Foscue E, Ellman JA, Nairn AC, Lombroso PJ. Inhibition of the tyrosine phosphatase STEP61 restores BDNF expression and reverses motor and cognitive deficits in phencyclidine-treated mice. Cellular And Molecular Life Sciences 2015, 73: 1503-1514. PMID: 26450419, PMCID: PMC4801664, DOI: 10.1007/s00018-015-2057-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzothiepinsBrain-Derived Neurotrophic FactorCells, CulturedCognition DisordersCREB-Binding ProteinDown-RegulationMaleMiceMice, Inbred C57BLMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Motor ActivityNeuronsPhencyclidinePhosphorylationProtein Tyrosine PhosphatasesReceptors, N-Methyl-D-AspartateRNA InterferenceUbiquitinationConceptsBrain-derived neurotrophic factorBDNF expressionProtein tyrosine Phosphatase 61Cognitive deficitsPCP-induced reductionPCP-treated micePhencyclidine-treated micePCP-induced increasePCP-induced hyperlocomotionTyrosine phosphatase STEP61STEP61 levelsBDNF transcriptionNeurotrophic factorNMDAR antagonistsCortical culturesCortical neuronsCNS disordersSynaptic strengtheningPsychotic episodeRodent modelsBrain disordersPharmacologic inhibitionSTEP61SchizophreniaCognitive functioning
2014
Alterations in STriatal‐Enriched protein tyrosine Phosphatase expression, activation, and downstream signaling in early and late stages of the YAC128 Huntington's disease mouse model
Gladding CM, Fan J, Zhang LY, Wang L, Xu J, Li EH, Lombroso PJ, Raymond LA. Alterations in STriatal‐Enriched protein tyrosine Phosphatase expression, activation, and downstream signaling in early and late stages of the YAC128 Huntington's disease mouse model. Journal Of Neurochemistry 2014, 130: 145-159. PMID: 24588402, PMCID: PMC4065618, DOI: 10.1111/jnc.12700.Peer-Reviewed Original ResearchConceptsDisease mouse modelYAC128 Huntington's disease mouse modelHuntington's disease mouse modelYAC128 miceCalpain-mediated cleavageMitogen-activated protein kinaseMouse modelCalpain inhibitionProtein tyrosine Phosphatase 61Wild-type cortical neuronsP38 phosphorylationNMDA receptor traffickingSTEP61 levelsSynaptic dysfunctionNMDAR localizationP38 mitogen-activated protein kinaseStriatal apoptosisCortical neuronsExtracellular signal-regulated proteinApoptotic signalingMutant huntingtin proteinStriatal tissueStriatal neurodegenerationTransgenic miceCalcium homeostasisInhibition of striatal‐enriched tyrosine phosphatase 61 in the dorsomedial striatum is sufficient to increased ethanol consumption
Darcq E, Hamida SB, Wu S, Phamluong K, Kharazia V, Xu J, Lombroso P, Ron D. Inhibition of striatal‐enriched tyrosine phosphatase 61 in the dorsomedial striatum is sufficient to increased ethanol consumption. Journal Of Neurochemistry 2014, 129: 1024-1034. PMID: 24588427, PMCID: PMC4055745, DOI: 10.1111/jnc.12701.Peer-Reviewed Original ResearchMeSH KeywordsAlcohol DrinkingAnimalsAntibodies, BlockingBlotting, WesternChoice BehaviorDown-RegulationEnzyme InhibitorsGene Knockdown TechniquesImmunohistochemistryLentivirusMaleMiceMice, Inbred C57BLMotor ActivityNeostriatumPhosphorylationProtein Tyrosine PhosphatasesQuinineRNA, Small InterferingSaccharin
2010
The role of STEP in Alzheimer's disease
Kurup P, Zhang Y, Venkitaramani DV, Xu J, Lombroso PJ. The role of STEP in Alzheimer's disease. Channels 2010, 4: 347-350. PMID: 20699650, PMCID: PMC3230511, DOI: 10.4161/chan.4.5.12910.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate (NMDA) type glutamate receptorsAlzheimer's diseaseProtein tyrosine Phosphatase 61AD prefrontal cortexAD mouse modelType glutamate receptorsGlutamate receptor traffickingNeuronal surface membraneNMDAR internalizationAβ treatmentPutative causative agentGlutamate receptorsMouse modelCulture resultsGluN1/Prefrontal cortexDiseaseNeuronal membranesNMDAR endocytosisAdditional studiesAβCausative agentSurface expressionUbiquitin-proteasome systemReceptor complexAβ-Mediated NMDA Receptor Endocytosis in Alzheimer's Disease Involves Ubiquitination of the Tyrosine Phosphatase STEP61
Kurup P, Zhang Y, Xu J, Venkitaramani DV, Haroutunian V, Greengard P, Nairn AC, Lombroso PJ. Aβ-Mediated NMDA Receptor Endocytosis in Alzheimer's Disease Involves Ubiquitination of the Tyrosine Phosphatase STEP61. Journal Of Neuroscience 2010, 30: 5948-5957. PMID: 20427654, PMCID: PMC2868326, DOI: 10.1523/jneurosci.0157-10.2010.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAnimalsCell LineCells, CulturedCerebral CortexEndocytosisHumansIn Vitro TechniquesMiceMice, KnockoutMice, TransgenicMiddle AgedNeuronsProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateUbiquitinated ProteinsUbiquitinationConceptsAlzheimer's diseaseAbeta treatmentNR2B subunitProtein tyrosine Phosphatase 61Cognitive deficitsNMDA receptor internalizationHuman AD brainsMouse cortical culturesNR1/NR2B receptorsNMDA receptor endocytosisIonotropic glutamate receptorsTyrosine phosphatase STEP61AD brainCortical slicesCortical culturesGlutamate receptorsNR2B receptorsPostsynaptic terminalsPrefrontal cortexNeuronal membranesElevated levelsCortexReceptor internalizationUbiquitin-proteasome systemStep activity