Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3.1 essential for mGluR-LTD.
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Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3.1 essential for mGluR-LTD. / Park, Sungjin; Park, Joo Min; Kim, Sangmok; Kim, Jin-Ah; Shepherd, Jason D; Smith-Hicks, Constance L; Chowdhury, Shoaib; Kaufmann, Walter; Kuhl, Dietmar; Ryazanov, Alexey G; Huganir, Richard L; Linden, David J; Worley, Paul F.
In: NEURON, Vol. 59, No. 1, 1, 2008, p. 70-83.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3.1 essential for mGluR-LTD.
AU - Park, Sungjin
AU - Park, Joo Min
AU - Kim, Sangmok
AU - Kim, Jin-Ah
AU - Shepherd, Jason D
AU - Smith-Hicks, Constance L
AU - Chowdhury, Shoaib
AU - Kaufmann, Walter
AU - Kuhl, Dietmar
AU - Ryazanov, Alexey G
AU - Huganir, Richard L
AU - Linden, David J
AU - Worley, Paul F
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 59
SP - 70
EP - 83
JO - NEURON
JF - NEURON
SN - 0896-6273
IS - 1
M1 - 1
ER -