{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1362825895660476544.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1523/jneurosci.3871-05.2005"}},{"identifier":{"@type":"URI","@value":"https://syndication.highwire.org/content/doi/10.1523/JNEUROSCI.3871-05.2005"}}],"dc:title":[{"@value":"Modulation of NMDA Receptors by Pituitary Adenylate Cyclase Activating Peptide in CA1 Neurons Requires Gα<sub>q</sub>, Protein Kinase C, and Activation of Src"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>At CA1 synapses, activation of NMDA receptors (NMDARs) is required for the induction of both long-term potentiation and depression. The basal level of activity of these receptors is controlled by converging cell signals from G-protein-coupled receptors and receptor tyrosine kinases. Pituitary adenylate cyclase activating peptide (PACAP) is implicated in the regulation of synaptic plasticity because it enhances NMDAR responses by stimulating Gα<jats:sub>s</jats:sub>-coupled receptors and protein kinase A (Yaka et al., 2003). However, the major hippocampal PACAP1 receptor (PAC<jats:sub>1</jats:sub>R) also signals via Gα<jats:sub>q</jats:sub>subunits and protein kinase C (PKC). In CA1 neurons, we showed that PACAP38 (1 n<jats:sc>m</jats:sc>) enhanced synaptic NMDA, and evoked NMDAR, currents in isolated CA1 neurons via activation of the PAC<jats:sub>1</jats:sub>R, Gα<jats:sub>q</jats:sub>, and PKC. The signaling was blocked by intracellular applications of the Src inhibitory peptide Src(40-58). Immunoblots confirmed that PACAP38 biochemically activates Src. A Gα<jats:sub>q</jats:sub>pathway is responsible for this Src-dependent PACAP enhancement because it was attenuated in mice lacking expression of phospholipase C β1, it was blocked by preventing elevations in intracellular Ca<jats:sup>2+</jats:sup>, and it was eliminated by inhibiting either PKC or cell adhesion kinase β [CAKβ or Pyk2 (proline rich tyrosine kinase 2)]. Peptides that mimic the binding sites for either Fyn or Src on receptor for activated C kinase-1 (RACK1) also enhanced NMDAR in CA1 neurons, but their effects were blocked by Src(40-58), implying that Src is the ultimate regulator of NMDARs. RACK1 serves as a hub for PKC, Fyn, and Src and facilitates the regulation of basal NMDAR activity in CA1 hippocampal neurons.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380587973205246893","@type":"Researcher","foaf:name":[{"@value":"D. S. Macdonald"}]},{"@id":"https://cir.nii.ac.jp/crid/1380016869577647620","@type":"Researcher","foaf:name":[{"@value":"M. Weerapura"}]},{"@id":"https://cir.nii.ac.jp/crid/1380016869577647616","@type":"Researcher","foaf:name":[{"@value":"M. A. Beazely"}]},{"@id":"https://cir.nii.ac.jp/crid/1380016869577647621","@type":"Researcher","foaf:name":[{"@value":"L. Martin"}]},{"@id":"https://cir.nii.ac.jp/crid/1380016869577647619","@type":"Researcher","foaf:name":[{"@value":"W. Czerwinski"}]},{"@id":"https://cir.nii.ac.jp/crid/1380016869577647622","@type":"Researcher","foaf:name":[{"@value":"J. C. Roder"}]},{"@id":"https://cir.nii.ac.jp/crid/1380016869577647618","@type":"Researcher","foaf:name":[{"@value":"B. A. Orser"}]},{"@id":"https://cir.nii.ac.jp/crid/1380016869577647617","@type":"Researcher","foaf:name":[{"@value":"J. F. MacDonald"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"02706474"},{"@type":"EISSN","@value":"15292401"}],"prism:publicationName":[{"@value":"The Journal of Neuroscience"}],"dc:publisher":[{"@value":"Society for Neuroscience"}],"prism:publicationDate":"2005-12-07","prism:volume":"25","prism:number":"49","prism:startingPage":"11374","prism:endingPage":"11384"},"reviewed":"false","dc:rights":["https://creativecommons.org/licenses/by-nc-sa/4.0/"],"url":[{"@id":"https://syndication.highwire.org/content/doi/10.1523/JNEUROSCI.3871-05.2005"}],"createdAt":"2005-12-07","modifiedAt":"2025-01-06","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360005516725279872","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Muscarinic receptor stimulation induces TASK1 channel endocytosis through a PKC-Pyk2-Src pathway in PC12 cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360025429407266816","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Administration of a Selective Antagonist for Pituitary Adenylate Cyclase‐Activating Polypeptide Receptor in the Hippocampus Causes Anxiolytic Effects in the Male Rat"}]},{"@id":"https://cir.nii.ac.jp/crid/1360565166743045376","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Metaplasticity gated through differential regulation of GluN2A versus GluN2B receptors by Src family kinases"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846644601741440","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Neuromodulatory Effect of Gα<sub>s</sub>- or Gα<sub>q</sub>-Coupled G-Protein-Coupled Receptor on NMDA Receptor Selectively Activates the NMDA Receptor/Ca<sup>2+</sup>/Calcineurin/cAMP Response Element-Binding Protein-Regulated Transcriptional Coactivator 1 Pathway to Effectively Induce Brain-Derived Neurotrophic Factor Expression in Neurons"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001206126703616","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"遺伝子発現屋の脳神経科学"},{"@language":"en","@value":"Gene Regulation Involved in the Formation of Long-term Memory"},{"@language":"ja-Kana","@value":"イデンシ ハツゲンヤ ノ ノウ シンケイ カガク"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282681194150272","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"神経可塑性の分子基盤を担う遺伝子発現制御系の解明"},{"@language":"en","@value":"Studies of Neuronal Gene Regulation Controlling the Molecular Mechanisms Underlying Neural Plasticity"},{"@language":"ja-Kana","@value":"シンケイ カソセイ ノ ブンシ キバン オ ニナウ イデンシ ハツゲン セイギョケイ ノ カイメイ"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1523/jneurosci.3871-05.2005"},{"@type":"CROSSREF","@value":"10.1002/npr2.12514_references_DOI_JRTmPGPguO3w86IkVObQYewiYYA"},{"@type":"CROSSREF","@value":"10.1248/yakushi.14-00241_references_DOI_JRTmPGPguO3w86IkVObQYewiYYA"},{"@type":"CROSSREF","@value":"10.1248/yakushi.17-00107_references_DOI_JRTmPGPguO3w86IkVObQYewiYYA"},{"@type":"CROSSREF","@value":"10.1038/emboj.2011.453_references_DOI_JRTmPGPguO3w86IkVObQYewiYYA"},{"@type":"CROSSREF","@value":"10.1523/jneurosci.3650-14.2015_references_DOI_JRTmPGPguO3w86IkVObQYewiYYA"},{"@type":"CROSSREF","@value":"10.1016/j.cellsig.2019.109434_references_DOI_JRTmPGPguO3w86IkVObQYewiYYA"}]}