Translational Control by MAPK Signaling in Long-Term Synaptic Plasticity and Memory
Enduring forms of synaptic plasticity and memory require new protein synthesis, but little is known about the underlying regulatory mechanisms. Here, we investigate the role of MAPK signaling in these processes. Conditional expression of a dominant-negative form of MEK1 in the postnatal murine foreb...
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| Veröffentlicht in: | Cell 2004-02, Vol.116 (3), p.467-479 |
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| creator | Kelleher, Raymond J Govindarajan, Arvind Jung, Hae-Yoon Kang, Hyejin Tonegawa, Susumu |
| description | Enduring forms of synaptic plasticity and memory require new protein synthesis, but little is known about the underlying regulatory mechanisms. Here, we investigate the role of MAPK signaling in these processes. Conditional expression of a dominant-negative form of MEK1 in the postnatal murine forebrain inhibited ERK activation and caused selective deficits in hippocampal memory retention and the translation-dependent, transcription-independent phase of hippocampal L-LTP. In hippocampal neurons, ERK inhibition blocked neuronal activity-induced translation as well as phosphorylation of the translation factors eIF4E, 4EBP1, and ribosomal protein S6. Correspondingly, protein synthesis and translation factor phosphorylation induced in control hippocampal slices by L-LTP-generating tetanization were significantly reduced in mutant slices. Translation factor phosphorylation induced in the control hippocampus by memory formation was similarly diminished in the mutant hippocampus. These results suggest a crucial role for translational control by MAPK signaling in long-lasting forms of synaptic plasticity and memory. |
| doi_str_mv | 10.1016/S0092-8674(04)00115-1 |
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Here, we investigate the role of MAPK signaling in these processes. Conditional expression of a dominant-negative form of MEK1 in the postnatal murine forebrain inhibited ERK activation and caused selective deficits in hippocampal memory retention and the translation-dependent, transcription-independent phase of hippocampal L-LTP. In hippocampal neurons, ERK inhibition blocked neuronal activity-induced translation as well as phosphorylation of the translation factors eIF4E, 4EBP1, and ribosomal protein S6. Correspondingly, protein synthesis and translation factor phosphorylation induced in control hippocampal slices by L-LTP-generating tetanization were significantly reduced in mutant slices. Translation factor phosphorylation induced in the control hippocampus by memory formation was similarly diminished in the mutant hippocampus. 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| subjects | Animals Animals, Newborn Carrier Proteins - genetics Carrier Proteins - metabolism Cells, Cultured Enzyme Inhibitors - pharmacology Eukaryotic Initiation Factor-4E - genetics Eukaryotic Initiation Factor-4E - metabolism Gene Expression Regulation, Enzymologic - genetics Hippocampus - cytology Hippocampus - enzymology Hippocampus - growth & development In Vitro Techniques Long-Term Potentiation - drug effects Long-Term Potentiation - physiology MAP Kinase Kinase 1 MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - physiology Memory - drug effects Memory - physiology Memory Disorders - enzymology Memory Disorders - genetics Mice Mice, Transgenic Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinase Kinases - genetics Mitogen-Activated Protein Kinase Kinases - metabolism Mitogen-Activated Protein Kinases - genetics Mitogen-Activated Protein Kinases - metabolism Mutation - genetics Neuronal Plasticity - physiology Phosphoproteins - genetics Phosphoproteins - metabolism Phosphorylation - drug effects Protein Biosynthesis - physiology Rats Ribosomal Protein S6 - genetics Ribosomal Protein S6 - metabolism Synapses - drug effects Synapses - enzymology Synapses - ultrastructure |
| title | Translational Control by MAPK Signaling in Long-Term Synaptic Plasticity and Memory |
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