Show simple item record

dc.contributor.authorXu, J
dc.contributor.authorHartley, BJ
dc.contributor.authorKurup, P
dc.contributor.authorPhillips, A
dc.contributor.authorTopol, A
dc.contributor.authorXu, M
dc.contributor.authorOnonenyi, C
dc.contributor.authorFoscue, E
dc.contributor.authorHo, S-M
dc.contributor.authorBaguley, TD
dc.contributor.authorCarty, N
dc.contributor.authorBarros, Claudia
dc.contributor.authorMüller, U
dc.contributor.authorGupta, S
dc.contributor.authorGochman, P
dc.contributor.authorRapoport, J
dc.contributor.authorEllman, JA
dc.contributor.authorPittenger, C
dc.contributor.authorAronow, B
dc.contributor.authorNairn, AC
dc.contributor.authorNestor, MW
dc.contributor.authorLombroso, PJ
dc.contributor.authorBrennand, KJ
dc.date.accessioned2016-10-26T21:27:12Z
dc.date.accessioned2017-08-10T11:27:15Z
dc.date.available2016-10-26T21:27:12Z
dc.date.available2017-08-10T11:27:15Z
dc.date.issued2016-10-18
dc.identifier.issn1359-4184
dc.identifier.issn1476-5578
dc.identifier.urihttp://hdl.handle.net/10026.1/9726
dc.description.abstract

The brain-specific tyrosine phosphatase, STEP (STriatal-Enriched protein tyrosine Phosphatase) is an important regulator of synaptic function. STEP normally opposes synaptic strengthening by increasing N-methyl D-aspartate glutamate receptor (NMDAR) internalization through dephosphorylation of GluN2B and inactivation of the kinases extracellular signal-regulated kinase 1/2 and Fyn. Here we show that STEP61 is elevated in the cortex in the Nrg1+/- knockout mouse model of schizophrenia (SZ). Genetic reduction or pharmacological inhibition of STEP prevents the loss of NMDARs from synaptic membranes and reverses behavioral deficits in Nrg1+/- mice. STEP61 protein is also increased in cortical lysates from the central nervous system-specific ErbB2/4 mouse model of SZ, as well as in human induced pluripotent stem cell (hiPSC)-derived forebrain neurons and Ngn2-induced excitatory neurons, from two independent SZ patient cohorts. In these selected SZ models, increased STEP61 protein levels likely reflect reduced ubiquitination and degradation. These convergent findings from mouse and hiPSC SZ models provide evidence for STEP61 dysfunction in SZ.

dc.format.extent271-281
dc.format.mediumPrint-Electronic
dc.languageen
dc.language.isoen
dc.publisherSpringer Science and Business Media LLC
dc.relation.replaceshttp://hdl.handle.net/10026.1/6643
dc.relation.replaces10026.1/6643
dc.subjectAnimals
dc.subjectDisease Models, Animal
dc.subjectFemale
dc.subjectHumans
dc.subjectInduced Pluripotent Stem Cells
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMice, Knockout
dc.subjectNeuregulin-1
dc.subjectNeurons
dc.subjectPhosphorylation
dc.subjectProtein Tyrosine Phosphatases
dc.subjectRats
dc.subjectReceptors, N-Methyl-D-Aspartate
dc.subjectSchizophrenia
dc.subjectUbiquitination
dc.titleInhibition of STEP61 ameliorates deficits in mouse and hiPSC-based schizophrenia models
dc.typejournal-article
dc.typeJournal Article
dc.typeResearch Support, N.I.H., Extramural
dc.typeResearch Support, Non-U.S. Gov't
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000423441700013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue2
plymouth.volume23
plymouth.publication-statusPublished
plymouth.journalMolecular Psychiatry
dc.identifier.doi10.1038/mp.2016.163
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/Peninsula Medical School
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
plymouth.organisational-group/Plymouth/Users by role/Researchers in ResearchFish submission
dc.publisher.placeEngland
dcterms.dateAccepted2016-08-11
dc.identifier.eissn1476-5578
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1038/mp.2016.163
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-10-18
rioxxterms.typeJournal Article/Review
plymouth.oa-locationhttp://www.nature.com/mp/journal/vaop/ncurrent/pdf/mp2016163a.pdf


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record


All items in PEARL are protected by copyright law.
Author manuscripts deposited to comply with open access mandates are made available in accordance with publisher policies. Please cite only the published version using the details provided on the item record or document. In the absence of an open licence (e.g. Creative Commons), permissions for further reuse of content should be sought from the publisher or author.
Theme by 
Atmire NV