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http://purl.uniprot.org/citations/19726651http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19726651http://www.w3.org/2000/01/rdf-schema#comment"Evidence suggests that NMDA-type glutamate receptors contribute to degeneration of striatal medium-sized spiny neurons (MSNs) in Huntington's disease (HD). Previously, we demonstrated that NMDA receptor (NMDAR)-mediated current and/or toxicity is increased in MSNs from the yeast artificial chromosome (YAC) transgenic mouse model expressing polyglutamine (polyQ)-expanded (mutant) full-length human huntingtin (htt). Others have shown that membrane-associated guanylate kinases (MAGUKs), such as PSD-95 and SAP102, modulate NMDAR surface expression and excitotoxicity in hippocampal and cortical neurons and that htt interacts with PSD-95. Here, we tested the hypothesis that an altered association between MAGUKs and NMDARs in mutant huntingtin-expressing cells contributes to increased susceptibility to excitotoxicity. We show that htt coimmunoprecipitated with SAP102 in HEK293T cells and striatal tissue from wild-type and YAC transgenic mice; however, the association of SAP102 with htt or the NMDAR NR2B subunit was unaffected by htt polyQ length, whereas association of PSD-95 with NR2B in striatal tissue was enhanced by increased htt polyQ length. Treatment of cultured MSNs with Tat-NR2B9c peptide blocked binding of NR2B with SAP102 and PSD-95 and reduced NMDAR surface expression by 20% in both YAC transgenic and wild-type MSNs, and also restored susceptibility to NMDAR excitoxicity in YAC HD MSNs to levels observed in wild-type MSNs; a similar effect on excitotoxicity was observed after knockdown of PSD-95 by small interfering RNA. Unlike previous findings in cortical and hippocampal neurons, rescue of NMDA toxicity by Tat-NR2B9c occurred independently of any effect on neuronal nitric oxide synthase activity. Our results elucidate further the mechanisms underlying enhanced excitotoxicity in HD."xsd:string
http://purl.uniprot.org/citations/19726651http://purl.org/dc/terms/identifier"doi:10.1523/jneurosci.2491-09.2009"xsd:string
http://purl.uniprot.org/citations/19726651http://purl.uniprot.org/core/author"Fan J."xsd:string
http://purl.uniprot.org/citations/19726651http://purl.uniprot.org/core/author"Zhang L.Y."xsd:string
http://purl.uniprot.org/citations/19726651http://purl.uniprot.org/core/author"Hayden M.R."xsd:string
http://purl.uniprot.org/citations/19726651http://purl.uniprot.org/core/author"Raymond L.A."xsd:string
http://purl.uniprot.org/citations/19726651http://purl.uniprot.org/core/author"Cowan C.M."xsd:string
http://purl.uniprot.org/citations/19726651http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19726651http://purl.uniprot.org/core/name"J Neurosci"xsd:string
http://purl.uniprot.org/citations/19726651http://purl.uniprot.org/core/pages"10928-10938"xsd:string
http://purl.uniprot.org/citations/19726651http://purl.uniprot.org/core/title"Interaction of postsynaptic density protein-95 with NMDA receptors influences excitotoxicity in the yeast artificial chromosome mouse model of Huntington's disease."xsd:string
http://purl.uniprot.org/citations/19726651http://purl.uniprot.org/core/volume"29"xsd:string
http://purl.uniprot.org/citations/19726651http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19726651
http://purl.uniprot.org/citations/19726651http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19726651
http://purl.uniprot.org/uniprot/#_A8K3C9-mappedCitation-19726651http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19726651
http://purl.uniprot.org/uniprot/#_B7Z3U2-mappedCitation-19726651http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19726651
http://purl.uniprot.org/uniprot/#_B7Z4H2-mappedCitation-19726651http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19726651
http://purl.uniprot.org/uniprot/#_B7Z647-mappedCitation-19726651http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19726651
http://purl.uniprot.org/uniprot/#_B9EGL1-mappedCitation-19726651http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19726651
http://purl.uniprot.org/uniprot/#_D2CTD2-mappedCitation-19726651http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19726651
http://purl.uniprot.org/uniprot/#_D2CTD4-mappedCitation-19726651http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19726651
http://purl.uniprot.org/uniprot/#_D2CTD5-mappedCitation-19726651http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19726651
http://purl.uniprot.org/uniprot/#_D2CTD6-mappedCitation-19726651http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19726651
http://purl.uniprot.org/uniprot/#_D2CTD7-mappedCitation-19726651http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19726651