title: Consolidation of transient ionotropic glutamate signals through nuclear transcription factors in the brain.
abstract: Long-lasting alterations of neuronal functions could involve mechanisms associated with consolidation of transient extracellular signals through modulation of de novo synthesis of particular functional proteins in the brain. In eukaryotes, protein de novo synthesis is mainly under the control at the level of gene transcription by transcription factors in the cell nucleus. Transcription factors are nuclear proteins with an ability to recognize particular core nucleotides at the upstream and/or downstream of target genes, and thereby to modulate the activity of RNA polymerase II that is responsible for the formation of mRNA from double stranded DNA. Gel retardation electrophoresis is widely employed for conventional detection of DNA binding activities of a variety of transcription factors with different protein motifs. Extracellular ionotropic glutamate (Glu) signals lead to rapid and selective potentiation of DNA binding of the nuclear transcription factor activator protein-1 (AP1) that is a homo- and heterodimeric complex between Jun and Fos family members, in addition to inducing expression of the corresponding proteins, in a manner unique to each Glu signal in murine hippocampus. Therefore, extracellular Glu signals may be differentially transduced into the nucleus to express AP1 with different assemblies between Jun and Fos family members, and thereby to modulate de novo synthesis of the individual target proteins at the level of gene transcription in the hippocampus. Such mechanisms may be operative on synaptic plasticity as well as delayed neuronal death through consolidation of alterations of a variety of cellular functions induced by transient extracellular signals in the brain.
authors.affiliation: Department of Molecular Pharmacology, Kanazawa University Faculty of Pharmaceutical Sciences, 13-1 Takara-machi, Kanazawa, 920-0934, Ishikawa, Japan. yyoneda@anet.ne.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Yoneda
authors.forename: N
authors.initials: N
authors.lastname: Kuramoto
authors.forename: T
authors.initials: T
authors.lastname: Kitayama
authors.forename: E
authors.initials: E
authors.lastname: Hinoi
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors