http://purl.uniprot.org/citations/19726651 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/19726651 | http://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/19726651 | http://purl.org/dc/terms/identifier | "doi:10.1523/jneurosci.2491-09.2009"xsd:string |
http://purl.uniprot.org/citations/19726651 | http://purl.uniprot.org/core/author | "Fan J."xsd:string |
http://purl.uniprot.org/citations/19726651 | http://purl.uniprot.org/core/author | "Zhang L.Y."xsd:string |
http://purl.uniprot.org/citations/19726651 | http://purl.uniprot.org/core/author | "Hayden M.R."xsd:string |
http://purl.uniprot.org/citations/19726651 | http://purl.uniprot.org/core/author | "Raymond L.A."xsd:string |
http://purl.uniprot.org/citations/19726651 | http://purl.uniprot.org/core/author | "Cowan C.M."xsd:string |
http://purl.uniprot.org/citations/19726651 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
http://purl.uniprot.org/citations/19726651 | http://purl.uniprot.org/core/name | "J Neurosci"xsd:string |
http://purl.uniprot.org/citations/19726651 | http://purl.uniprot.org/core/pages | "10928-10938"xsd:string |
http://purl.uniprot.org/citations/19726651 | http://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/19726651 | http://purl.uniprot.org/core/volume | "29"xsd:string |
http://purl.uniprot.org/citations/19726651 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19726651 |
http://purl.uniprot.org/citations/19726651 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/19726651 |
http://purl.uniprot.org/uniprot/#_A8K3C9-mappedCitation-19726651 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19726651 |
http://purl.uniprot.org/uniprot/#_B7Z3U2-mappedCitation-19726651 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19726651 |
http://purl.uniprot.org/uniprot/#_B7Z4H2-mappedCitation-19726651 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19726651 |
http://purl.uniprot.org/uniprot/#_B7Z647-mappedCitation-19726651 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19726651 |
http://purl.uniprot.org/uniprot/#_B9EGL1-mappedCitation-19726651 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19726651 |
http://purl.uniprot.org/uniprot/#_D2CTD2-mappedCitation-19726651 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19726651 |
http://purl.uniprot.org/uniprot/#_D2CTD4-mappedCitation-19726651 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19726651 |
http://purl.uniprot.org/uniprot/#_D2CTD5-mappedCitation-19726651 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19726651 |
http://purl.uniprot.org/uniprot/#_D2CTD6-mappedCitation-19726651 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19726651 |
http://purl.uniprot.org/uniprot/#_D2CTD7-mappedCitation-19726651 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19726651 |