title: Phosphorylation of eukaryotic translation initiation factor 4E and eukaryotic translation initiation factor 4E-binding protein (4EBP) and their upstream signaling components undergo diurnal oscillation in the mouse hippocampus: implications for memory persistence.
abstract: Translation of mRNA plays a critical role in consolidation of long-term memory. Here, we report that markers of initiation of mRNA translation are activated during training for contextual memory and that they undergo diurnal oscillation in the mouse hippocampus with maximal activity observed during the daytime (zeitgeber time 4-8 h). Phosphorylation and activation of eukaryotic translation initiation factor 4E (eIF4E), eIF4E-binding protein 1 (4EBP1), ribosomal protein S6, and eIF4F cap-complex formation, all of which are markers for translation initiation, were higher in the hippocampus during the daytime compared with night. The circadian oscillation in markers of mRNA translation was lost in memory-deficient transgenic mice lacking calmodulin-stimulated adenylyl cyclases. Moreover, disruption of the circadian rhythm blocked diurnal oscillations in eIF4E, 4EBP1, rpS6, Akt, and ERK1/2 phosphorylation and impaired memory consolidation. Furthermore, repeated inhibition of translation in the hippocampus 48 h after contextual training with the protein synthesis inhibitor anisomycin impaired memory persistence. We conclude that repeated activation of markers of translation initiation in hippocampus during the circadian cycle might be critical for memory persistence.
authors.affiliation: From the Departments of Pharmacology and.
authors.forename: Amit
authors.initials: A
authors.lastname: Saraf
authors.affiliation: From the Departments of Pharmacology and.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.affiliation: Biochemistry, University of Washington, Seattle, Washington 98195.
authors.forename: David R
authors.initials: DR
authors.lastname: Morris
authors.affiliation: From the Departments of Pharmacology and dstorm@u.washington.edu.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Storm
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000262:Adenylyl Cyclases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D057567:Memory, Long-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010442:Peptide Chain Initiation, Translational; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D038601:Ribosomal Protein S6 / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D010750:Phosphoproteins; D012333:RNA, Messenger; D038601:Ribosomal Protein S6; C448579:ribosomal protein S6, mouse; C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1; C118292:adenylyl cyclase 8
keywords: Circadian Rhythm; Contextual Fear Conditioning; Eukaryotic Translation Initiation Factor 4E (eIF4E); Long Term Memory; Neurobiology; Signal Transduction; Translation