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
2016
Inhibition of STEP61 ameliorates deficits in mouse and hiPSC-based schizophrenia models
Xu J, Hartley BJ, Kurup P, Phillips A, Topol A, Xu M, Ononenyi C, Foscue E, Ho SM, Baguley TD, Carty N, Barros CS, Müller U, Gupta S, Gochman P, Rapoport J, Ellman JA, Pittenger C, Aronow B, Nairn AC, Nestor MW, Lombroso PJ, Brennand KJ. Inhibition of STEP61 ameliorates deficits in mouse and hiPSC-based schizophrenia models. Molecular Psychiatry 2016, 23: 271-281. PMID: 27752082, PMCID: PMC5395367, DOI: 10.1038/mp.2016.163.Peer-Reviewed Original ResearchConceptsBrain-specific tyrosine phosphataseDephosphorylation of GluN2BExtracellular signal-regulated kinase 1/2Signal-regulated kinase 1/2Glutamate receptor internalizationPluripotent stem cellsKnockout mouse modelTyrosine phosphataseMouse modelKinase 1/2Receptor internalizationImportant regulatorGenetic reductionLoss of NMDARsStem cellsN-methyl DPharmacological inhibitionProtein levelsSynaptic functionSTEP61Patient cohortForebrain neuronsBehavioral deficitsExcitatory neuronsSchizophrenia model
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 functioningStriatal‐enriched protein tyrosine phosphatase regulates the PTPα/Fyn signaling pathway
Xu J, Kurup P, Foscue E, Lombroso PJ. Striatal‐enriched protein tyrosine phosphatase regulates the PTPα/Fyn signaling pathway. Journal Of Neurochemistry 2015, 134: 629-641. PMID: 25951993, PMCID: PMC4516628, DOI: 10.1111/jnc.13160.Peer-Reviewed Original ResearchConceptsProtein tyrosine phosphataseProtein kinase ARegulation of FynTyrosine phosphataseReceptor-type protein tyrosine phosphatase alphaProtein tyrosine phosphatase alphaStriatal-enriched protein tyrosine phosphataseRegulatory tyrosine residuesActivation of FynTyrosine kinase FynRegulatory tyrosineProtein tyrosinePTPαKinase FynSynaptic membranesKinase ATyrosine residuesFyn activityFynNovel substratePrimary neuronal culturesSTEP61Synergistic regulationMolecular techniquesNovel mechanismSTEP61 is a substrate of the E3 ligase parkin and is upregulated in Parkinson’s disease
Kurup PK, Xu J, Videira RA, Ononenyi C, Baltazar G, Lombroso PJ, Nairn AC. STEP61 is a substrate of the E3 ligase parkin and is upregulated in Parkinson’s disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 1202-1207. PMID: 25583483, PMCID: PMC4313846, DOI: 10.1073/pnas.1417423112.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCorpus StriatumCyclic AMP Response Element-Binding ProteinDown-RegulationGene Expression Regulation, EnzymologicHEK293 CellsHumansMAP Kinase Signaling SystemMiceMice, KnockoutMitogen-Activated Protein Kinase 3MPTP PoisoningProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, Sprague-DawleyUbiquitinationUbiquitin-Protein LigasesUp-RegulationConceptsE3 ubiquitin ligase ParkinSubstantia nigra pars compactaPathophysiology of PDProtein tyrosine phosphataseUbiquitin ligase ParkinSporadic Parkinson's diseaseE3 ligase ParkinRegulation of ParkinParkinson's diseaseTyrosine phosphataseParkin mutantsE3 ligaseProteasome systemDopaminergic neuronsDownstream targetsAutosomal recessive juvenile parkinsonismNovel substrateSTEP61ParkinCellular modelSTEP61 levelsSNc dopaminergic neuronsProtein levelsFunction contributesERK1/2