Journal
JOURNAL OF NEUROSCIENCE
Volume 26, Issue 8, Pages 2167-2173Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5196-05.2006
Keywords
protein synthesis; hippocampus; mGluR; ERK; synaptic plasticity; PI3 kinase
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Funding
- NHLBI NIH HHS [T32 HL07676] Funding Source: Medline
- NINDS NIH HHS [NS034007, NS047384] Funding Source: Medline
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Long-term depression (LTD) is an activity-dependent decrease in synaptic efficacy that can be induced in hippocampal area CA1 by pharmacological application of the selective group I metabotropic glutamate receptor (mGluR) agonist 3,5-diyhroxyphenylglycine ( DHPG). Recent work has demonstrated that DHPG-induced LTD recruits at least two signal transduction pathways known to couple to translation, the mitogen-activated protein kinase kinase (MEK) - extracellular signal-regulated kinase (ERK) signaling pathway and the phosphoinositide 3-kinase (PI3K) - Akt - mammalian target of rapamycin ( mTOR) signaling pathway. However, it remains unclear which translation factors are engaged by these two signaling pathways during mGluR-LTD. In this study, we investigated whether the group I mGluRs couple to the cap-dependent translation proteins: Mnk1, eIF4E, and 4E-BP. We found that both the MEK - ERK and PI3K - mTOR signaling pathways are critical for the DHPG-induced regulation of these translation factors. Furthermore, we demonstrate that increasing eIF4F complex availability via the genetic elimination of 4E-BP2 can enhance the degree of LTD achieved by DHPG application in an ERK-dependent manner. Our results provide direct evidence that cap-dependent translation is engaged during mGluR-LTD and demonstrate that the MEK - ERK and PI3K - mTOR signaling pathways converge to regulate eIF4E activity after induction of DHPG-LTD.
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