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 Ca2+/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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 70-83 |
| Number of pages | 14 |
| Journal | Neuron |
| Volume | 59 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 10 2008 |
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Keywords
- MOLNEURO
- PROTEINS
- SIGNALING
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
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 Leonie; Chowdhury, Shoaib; Kaufmann, Walter; Kuhl, Dietmar; Ryazanov, Alexey G.; Huganir, Richard L; Linden, David J; Worley, Paul F.
In: Neuron, Vol. 59, No. 1, 10.07.2008, p. 70-83.Research output: Contribution to journal › Article
}
TY - JOUR
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 Leonie
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 - 2008/7/10
Y1 - 2008/7/10
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 Ca2+/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 Ca2+/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.
KW - MOLNEURO
KW - PROTEINS
KW - SIGNALING
UR - http://www.scopus.com/inward/record.url?scp=46149087988&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=46149087988&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2008.05.023
DO - 10.1016/j.neuron.2008.05.023
M3 - Article
C2 - 18614030
AN - SCOPUS:46149087988
VL - 59
SP - 70
EP - 83
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 1
ER -