TY - JOUR T1 - Regulation of Eukaryotic Initiation Factor 4E by Converging Signaling Pathways during Metabotropic Glutamate Receptor-Dependent Long-Term Depression JF - The Journal of Neuroscience JO - J. Neurosci. SP - 2167 LP - 2173 DO - 10.1523/JNEUROSCI.5196-05.2006 VL - 26 IS - 8 AU - Jessica L. Banko AU - Lingfei Hou AU - Francis Poulin AU - Nahum Sonenberg AU - Eric Klann Y1 - 2006/02/22 UR - http://www.jneurosci.org/content/26/8/2167.abstract N2 - 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. ER -