ERK and mTOR signaling couple β-adrenergic receptors to translation initiation machinery to gate induction of protein synthesis-dependent long-term potentiation

Jennifer N. Gelinas, Jessica L. Banko, Lingfei Hou, Nahum Sonenberg, Edwin J. Weeber, Eric Klann, Peter V. Nguyen

Research output: Contribution to journalArticlepeer-review

Abstract

β-Adrenergic receptors critically modulate long-lasting synaptic plasticity and long-term memory in the mammalian hippocampus. Persistent long-term potentiation of synaptic strength requires protein synthesis and has been correlated with some forms of hippocampal long-term memory. However, the intracellular processes that initiate protein synthesis downstream of the β-adrenergic receptor are unidentified. Here we report that activation of β-adrenergic receptors recruits ERK and mammalian target of rapamycin signaling to facilitate longterm potentiation maintenance at the level of translation initiation. Treatment of mouse hippocampal slices with a β-adrenergic receptor agonist results in activation of eukaryotic initiation factor 4E and the eukaryotic initiation factor 4E kinase Mnk1, along with inhibition of the translation repressor 4E-BP. This coordinated activation of translation machinery requires concomitant ERK and mammalian target of rapamycin signaling. Taken together, our data identify distinct signaling pathways that converge to regulate β-adrenergic receptor-dependent protein synthesis during long-term synaptic potentiation in the hippocampus. We suggest that β-adrenergic receptors play a crucial role in gating the induction of long-lasting synaptic plasticity at the level of translation initiation, a mechanism that may underlie the ability of these receptors to influence the formation of long-lasting memories.

Original languageEnglish (US)
Pages (from-to)27527-27535
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number37
DOIs
StatePublished - Sep 14 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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