Regulation of eukaryotic initiation factor 4E by converging signaling pathways during metabotropic glutamate receptor-dependent long-term depression

Jessica L. Banko, Lingfei Hou, Francis Poulin, Nahum Sonenberg, Eric Klann

Research output: Contribution to journalArticle

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)-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.

Original languageEnglish (US)
Pages (from-to)2167-2173
Number of pages7
JournalJournal of Neuroscience
Volume26
Issue number8
DOIs
StatePublished - Feb 22 2006

Fingerprint

Eukaryotic Initiation Factor-4E
Metabotropic Glutamate Receptors
Mitogen-Activated Protein Kinase Kinases
1-Phosphatidylinositol 4-Kinase
Mitogen-Activated Protein Kinase 6
Sirolimus
Extracellular Signal-Regulated MAP Kinases
Excitatory Amino Acid Agonists
Critical Pathways
Protein Biosynthesis
Signal Transduction
Pharmacology

Keywords

  • ERK
  • Hippocampus
  • mGluR
  • PI3 kinase
  • Protein synthesis
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Regulation of eukaryotic initiation factor 4E by converging signaling pathways during metabotropic glutamate receptor-dependent long-term depression. / Banko, Jessica L.; Hou, Lingfei; Poulin, Francis; Sonenberg, Nahum; Klann, Eric.

In: Journal of Neuroscience, Vol. 26, No. 8, 22.02.2006, p. 2167-2173.

Research output: Contribution to journalArticle

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