EIF4B phosphorylation at Ser504 links synaptic activity with protein translation in physiology and pathology

B Bettegazzi, Serena Bellani, P Roncon, FC Guarnieri, A Bertero, F Codazzi, F Valtorta, M Simonato, F Grohovaz, D Zacchetti

Research output: Contribution to journalArticle

Abstract

Neuronal physiology requires activity-driven protein translation, a process in which translation initiation factors are key players. We focus on eukaryotic initiation factor 4B (eIF4B), a regulator of protein translation, whose function in neurons is undetermined. We show that neuronal activity affects eIF4B phosphorylation and identify Ser504 as a phosphorylation site regulated by casein kinases and sensitive to the activation of metabotropic glutamate receptors. Ser504 phosphorylation increases eIF4B recruitment to the pre-initiation complex and influences eIF4B localization at synapses. Moreover, Ser504 phosphorylation modulates the translation of protein kinase Mζ. Therefore, by sensing synaptic activity, eIF4B could adjust translation to neuronal needs, promoting adaptive changes in synaptic plasticity. We also show that Ser504 phosphorylation is increased in vivo in a rat model of epilepsy during epileptogenesis i.e. when translation drives maladaptive synaptic changes. We propose eIF4B as a mediator between neuronal activity and translation, with relevance in the control of synaptic plasticity. © 2017 The Author(s).
Original languageEnglish
Article number10563
JournalScientific Reports
Volume7
Issue number12
DOIs
Publication statusPublished - 2017

Fingerprint Dive into the research topics of 'EIF4B phosphorylation at Ser504 links synaptic activity with protein translation in physiology and pathology'. Together they form a unique fingerprint.

  • Cite this