ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Bidirectional regulation of eEF2 phosphorylation controls synaptic plasticity by decoding neuronal activity patterns.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Regulation of Translation by PKA Signaling Pathway.International journal of molecular sciences · 2026Review
- Translation stalling in neurons: a critical mechanism for timely protein delivery to distal cellular processes.Biochemical Society transactions · 2025Article
- Intrauterine phenotype, genetic analysis, and pregnancy follow-up of fetuses with the 16p12.2 microdeletion.Frontiers in genetics · 2025Article
- Molecular Genetic and Clinical Characteristics of Fetuses With Chromosome 16 Short-Arm Microdeletions/Microduplications.Journal of clinical laboratory analysis · 2024Article
- Multiomics of early epileptogenesis in mice reveals phosphorylation and dephosphorylation-directed growth and synaptic weakening.iScience · 2024Article
- Ribosomes in RNA Granules Are Stalled on mRNA Sequences That Are Consensus Sites for FMRP Association.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Ghrelin rapidly elevates protein synthesis in vitro by employing the rpS6K-eEF2K-eEF2 signalling axis.Cellular and molecular life sciences : CMLS · 2022Article
- The role of altered translation in intellectual disability and epilepsy.Progress in neurobiology · 2022Review
- Functionally distinct roles for eEF2K in the control of ribosome availability and p-body abundance.Nature communications · 2021Article
- Activity-Dependent Gene Expression in Neurons.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2021Review
- Functional assessment of the "two-hit" model for neurodevelopmental defects in Drosophila and X. laevis.PLoS genetics · 2021Article
- Insights Into the Pathologic Roles and Regulation of Eukaryotic Elongation Factor-2 Kinase.Frontiers in molecular biosciences · 2021Review
- Ribosome profiling in mouse hippocampus: plasticity-induced regulation and bidirectional control by TSC2 and FMRP.Molecular autism · 2020Article
- Article
- FMRP Control of Ribosome Translocation Promotes Chromatin Modifications and Alternative Splicing of Neuronal Genes Linked to Autism.Cell reports · 2020Article
- Cataloguing and Selection of mRNAs Localized to Dendrites in Neurons and Regulated by RNA-Binding Proteins in RNA Granules.Biomolecules · 2020Review
- Direct Medial Entorhinal Cortex Input to Hippocampal CA3 Is Crucial for eEF2K Inhibitor-Induced Neuronal Oscillations in the Mouse Hippocampus.Frontiers in cellular neuroscience · 2020Article
- Isoform Specificity of PKMs during Long-Term Facilitation inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Translational Control in the Brain in Health and Disease.Cold Spring Harbor perspectives in biology · 2019Review
- Assessment of complementarity of WGCNA and NERI results for identification of modules associated to schizophrenia spectrum disorders.PloS one · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
At the sensory-motor neuron synapse of Aplysia, either spaced or continuous (massed) exposure to serotonin (5-HT) induces a form of intermediate-term facilitation (ITF) that requires new protein synthesis but not gene transcription. However, spaced and massed ITF use distinct molecular mechanisms to maintain increased synaptic strength. Synapses activated by spaced applications of 5-HT generate an ITF that depends on persistent protein kinase A (PKA) activity, whereas an ITF produced by massed 5-HT depends on persistent protein kinase C (PKC) activity. In this study, we demonstrate that eukaryotic elongation factor 2 (eEF2), which catalyzes the GTP-dependent translocation of the ribosome during protein synthesis, acts as a biochemical sensor that is tuned to the pattern of neuronal stimulation. Specifically, we find that massed training leads to a PKC-dependent increase in phosphorylation of eEF2, whereas spaced training results in a PKA-dependent decrease in phosphorylation of eEF2. Importantly, by using either pharmacological or dominant-negative strategies to inhibit eEF2 kinase (eEF2K), we were able to block massed 5-HT-dependent increases in eEF2 phosphorylation and subsequent PKC-dependent ITF. In contrast, pharmacological inhibition of eEF2K during the longer period of time required for spaced training was sufficient to reduce eEF2 phosphorylation and induce ITF. Finally, we find that the massed 5-HT-dependent increase in synaptic strength requires translation elongation, but not translation initiation, whereas the spaced 5-HT-dependent increase in synaptic strength is partially dependent on translation initiation. Thus, bidirectional regulation of eEF2 is critical for decoding distinct activity patterns at synapses by activating distinct modes of translation regulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.