Neuron (Cambridge, Mass.), 2008-07, Vol.59 (1), p.70-83
2008
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- Autor(en) / Beteiligte
- Titel
- Elongation Factor 2 and Fragile X Mental Retardation Protein Control the Dynamic Translation of Arc/Arg3.1 Essential for mGluR-LTD
- Ist Teil von
- Neuron (Cambridge, Mass.), 2008-07, Vol.59 (1), p.70-83
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2008
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Group I metabotropic glutamate receptors (mGluR) induce long-term depression (LTD) that requires protein synthesis. Here, we demonstrate that Arc/Arg3.1 is translationally induced within 5 min of mGluR activation, and this response is essential for mGluR-dependent LTD. The increase in Arc/Arg3.1 translation requires eEF2K, a Ca 2+/calmodulin-dependent kinase that binds mGluR and dissociates upon mGluR activation, whereupon it phosphorylates eEF2. Phospho-eEF2 acts to slow the elongation step of translation and inhibits general protein synthesis but simultaneously increases Arc/Arg3.1 translation. Genetic deletion of eEF2K results in a selective deficit of rapid mGluR-dependent Arc/Arg3.1 translation and mGluR-LTD. This rapid translational mechanism is disrupted in the fragile X disease mouse ( Fmr1 KO) in which mGluR-LTD does not require de novo protein synthesis but does require Arc/Arg3.1. We propose a model in which eEF2K-eEF2 and FMRP coordinately control the dynamic translation of Arc/Arg3.1 mRNA in dendrites that is critical for synapse-specific LTD.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0896-6273eISSN: 1097-4199DOI: 10.1016/j.neuron.2008.05.023Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2743934
- Format
- –
- Schlagworte
- Animals, Animals, Newborn, Cell culture, Cells, Cultured, Cycloheximide - pharmacology, Cytoskeletal Proteins - metabolism, Dose-Response Relationship, Radiation, Electric Stimulation - methods, Excitatory Amino Acid Agents - pharmacology, Excitatory Postsynaptic Potentials - drug effects, Excitatory Postsynaptic Potentials - physiology, Excitatory Postsynaptic Potentials - radiation effects, Fragile X Mental Retardation Protein - genetics, Fragile X Mental Retardation Protein - physiology, Gene Expression Regulation - drug effects, Gene Expression Regulation - radiation effects, Hippocampus - cytology, In Vitro Techniques, Kinases, Long-Term Potentiation - physiology, Male, Mice, Mice, Knockout, Models, Biological, MOLNEURO, Nerve Tissue Proteins - metabolism, Neurons, Neurons - physiology, Patch-Clamp Techniques, Peptide Elongation Factor 2 - physiology, Protein Biosynthesis - drug effects, Protein Biosynthesis - physiology, Protein Biosynthesis - radiation effects, Protein synthesis, Protein Synthesis Inhibitors - pharmacology, Protein Transport - drug effects, Protein Transport - physiology, PROTEINS, Receptors, AMPA - physiology, SIGNALING, Studies