| Literature DB >> 18614030 |
Sungjin Park1, Joo Min Park, Sangmok Kim, Jin-Ah Kim, Jason D Shepherd, Constance L Smith-Hicks, Shoaib Chowdhury, Walter Kaufmann, Dietmar Kuhl, Alexey G Ryazanov, Richard L Huganir, David J Linden, Paul F Worley.
Abstract
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.Entities:
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Year: 2008 PMID： 18614030 PMCID： PMC2743934 DOI： 10.1016/j.neuron.2008.05.023
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173