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 journalArticle

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

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Long-Term Potentiation
Adrenergic Receptors
Machinery
Eukaryotic Initiation Factor-4E
Neuronal Plasticity
Long-Term Memory
Chemical activation
Sirolimus
Proteins
Data storage equipment
Plasticity
Hippocampus
Adrenergic Agonists
Aptitude
Phosphotransferases
Maintenance

ASJC Scopus subject areas

  • Biochemistry

Cite this

ERK and mTOR signaling couple β-adrenergic receptors to translation initiation machinery to gate induction of protein synthesis-dependent long-term potentiation. / Gelinas, Jennifer N.; Banko, Jessica L.; Hou, Lingfei; Sonenberg, Nahum; Weeber, Edwin J.; Klann, Eric; Nguyen, Peter V.

In: Journal of Biological Chemistry, Vol. 282, No. 37, 14.09.2007, p. 27527-27535.

Research output: Contribution to journalArticle

Gelinas, Jennifer N. ; Banko, Jessica L. ; Hou, Lingfei ; Sonenberg, Nahum ; Weeber, Edwin J. ; Klann, Eric ; Nguyen, Peter V. / ERK and mTOR signaling couple β-adrenergic receptors to translation initiation machinery to gate induction of protein synthesis-dependent long-term potentiation. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 37. pp. 27527-27535.
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