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dc.contributor.author | Nagura, Hitoshi | en |
dc.contributor.author | Ishikawa, Yasuyuki | en |
dc.contributor.author | Kobayashi, Katsunori | en |
dc.contributor.author | Takao, Keizo | en |
dc.contributor.author | Tanaka, Tomo | en |
dc.contributor.author | Nishikawa, Kouki | en |
dc.contributor.author | Tamura, Hideki | en |
dc.contributor.author | Shiosaka, Sadao | en |
dc.contributor.author | Suzuki, Hidenori | en |
dc.contributor.author | Miyakawa, Tsuyoshi | en |
dc.contributor.author | Fujiyoshi, Yoshinori | en |
dc.contributor.author | Doi, Tomoko | en |
dc.contributor.alternative | 土井, 知子 | ja |
dc.date.accessioned | 2013-09-03T07:11:21Z | - |
dc.date.available | 2013-09-03T07:11:21Z | - |
dc.date.issued | 2012-12-26 | - |
dc.identifier.issn | 1756-6606 | - |
dc.identifier.uri | http://hdl.handle.net/2433/178671 | - |
dc.description.abstract | [Background]Postsynaptic density (PSD)-95-like membrane-associated guanylate kinases (PSD-MAGUKs) are scaffold proteins in PSDs that cluster signaling molecules near NMDA receptors. PSD-MAGUKs share a common domain structure, including three PDZ (PDZ1/2/3) domains in their N-terminus. While multiple domains enable the PSD-MAGUKs to bind various ligands, the contribution of each PDZ domain to synaptic organization and function is not fully understood. Here, we focused on the PDZ1/2 domains of PSD-95 that bind NMDA-type receptors, and studied the specific roles of the ligand binding of these domains in the assembly of PSD proteins, synaptic properties of hippocampal neurons, and behavior, using ligand binding-deficient PSD-95 cDNA knockin (KI) mice. [Results]The KI mice showed decreased accumulation of mutant PSD-95, PSD-93 and AMPA receptor subunits in the PSD fraction of the hippocampus. In the hippocampal CA1 region of young KI mice, basal synaptic efficacy was reduced and long-term potentiation (LTP) was enhanced with intact long-term depression. In adult KI mice, there was no significant change in the magnitude of LTP in CA1, but robustly enhanced LTP was induced at the medial perforant path-dentate gyrus synapses, suggesting that PSD-95 has an age- and subregion-dependent role. In a battery of behavioral tests, KI mice showed markedly abnormal anxiety-like behavior, impaired spatial reference and working memory, and impaired remote memory and pattern separation in fear conditioning test. [Conclusions]These findings reveal that PSD-95 including its ligand binding of the PDZ1/2 domains controls the synaptic clustering of PSD-MAGUKs and AMPA receptors, which may have an essential role in regulating hippocampal synaptic transmission, plasticity, and hippocampus-dependent behavior. | en |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | BioMed Central Ltd. | en |
dc.rights | © 2012 Nagura et al.; licensee BioMed Central Ltd. | en |
dc.rights | This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. | en |
dc.subject | PSD-MAGUK | en |
dc.subject | Synaptic clustering | en |
dc.subject | PDZ domain | en |
dc.subject | PSD-95 | en |
dc.subject | Synaptic transmission | en |
dc.subject | Dentate gyrus | en |
dc.subject | Behavioral test battery | en |
dc.subject.mesh | Aging/physiology | en |
dc.subject.mesh | Animals | en |
dc.subject.mesh | Anxiety/pathology | en |
dc.subject.mesh | Anxiety/physiopathology | en |
dc.subject.mesh | Behavior, Animal | en |
dc.subject.mesh | Fear/physiology | en |
dc.subject.mesh | Gene Knock-In Techniques | en |
dc.subject.mesh | Green Fluorescent Proteins/metabolism | en |
dc.subject.mesh | Guanylate Kinase/chemistry | en |
dc.subject.mesh | Guanylate Kinase/metabolism | en |
dc.subject.mesh | Hippocampus/pathology | en |
dc.subject.mesh | Hippocampus/physiopathology | en |
dc.subject.mesh | Learning | en |
dc.subject.mesh | Ligands | en |
dc.subject.mesh | Long-Term Potentiation/physiology | en |
dc.subject.mesh | Long-Term Synaptic Depression/physiology | en |
dc.subject.mesh | Membrane Proteins/chemistry | en |
dc.subject.mesh | Membrane Proteins/metabolism | en |
dc.subject.mesh | Memory/physiology | en |
dc.subject.mesh | Mice | en |
dc.subject.mesh | Mice, Inbred C57BL | en |
dc.subject.mesh | Nerve Tissue Proteins/metabolism | en |
dc.subject.mesh | Neurons/metabolism | en |
dc.subject.mesh | Neurons/pathology | en |
dc.subject.mesh | Protein Structure, Tertiary | en |
dc.subject.mesh | Synapses/pathology | en |
dc.subject.mesh | Synaptic Transmission/physiology | en |
dc.title | Impaired synaptic clustering of postsynaptic density proteins and altered signal transmission in hippocampal neurons, and disrupted learning behavior in PDZ1 and PDZ2 ligand binding-deficient PSD-95 knockin mice. | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | Molecular brain | en |
dc.identifier.volume | 5 | - |
dc.relation.doi | 10.1186/1756-6606-5-43 | - |
dc.textversion | publisher | - |
dc.identifier.artnum | 43 | - |
dc.identifier.pmid | 23268962 | - |
dcterms.accessRights | open access | - |
出現コレクション: | 学術雑誌掲載論文等 |
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