@article {Banko2167, author = {Jessica L. Banko and Lingfei Hou and Francis Poulin and Nahum Sonenberg and Eric Klann}, title = {Regulation of Eukaryotic Initiation Factor 4E by Converging Signaling Pathways during Metabotropic Glutamate Receptor-Dependent Long-Term Depression}, volume = {26}, number = {8}, pages = {2167--2173}, year = {2006}, doi = {10.1523/JNEUROSCI.5196-05.2006}, publisher = {Society for Neuroscience}, abstract = {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){\textendash}extracellular signal-regulated kinase (ERK) signaling pathway and the phosphoinositide 3-kinase (PI3K){\textendash}Akt{\textendash}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{\textendash}ERK and PI3K{\textendash}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{\textendash}ERK and PI3K{\textendash}mTOR signaling pathways converge to regulate eIF4E activity after induction of DHPG-LTD.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/26/8/2167}, eprint = {https://www.jneurosci.org/content/26/8/2167.full.pdf}, journal = {Journal of Neuroscience} }