ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Dynamics of elongation factor 2 kinase regulation in cortical neurons in response to synaptic activity.
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 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- eEF2K as an important kinase associated with cancer survival and prognosis.Scientific reports · 2024Article
- Whole-brain mapping in adult zebrafish and identification of a novel tank test functional connectome.bioRxiv : the preprint server for biology · 2024Article
- Distinct calcium sources regulate temporal profiles of NMDAR and mGluR-mediated protein synthesis.Life science alliance · 2024Article
- eEF2K Inhibitor Design: The Progression of Exemplary Structure-Based Drug Design.Molecules (Basel, Switzerland) · 2023Review
- Spatiotemporally resolved protein synthesis as a molecular framework for memory consolidation.Trends in neurosciences · 2022Review
- Functionally distinct roles for eEF2K in the control of ribosome availability and p-body abundance.Nature communications · 2021Article
- The phosphorylation status of eukaryotic elongation factor-2 indicates neural activity in the brain.Molecular brain · 2021Article
- Inhibition of eEF2K synergizes with glutaminase inhibitors or 4EBP1 depletion to suppress growth of triple-negative breast cancer cells.Scientific reports · 2021Article
- Finding new edges: systems approaches to MTOR signaling.Biochemical Society transactions · 2021Review
- Insights Into the Pathologic Roles and Regulation of Eukaryotic Elongation Factor-2 Kinase.Frontiers in molecular biosciences · 2021Review
- AIMTOR, a BRET biosensor for live imaging, reveals subcellular mTOR signaling and dysfunctions.BMC biology · 2020Article
- D1 Dopamine Receptor Activation Induces Neuronal eEF2 Pathway-Dependent Protein Synthesis.Frontiers in molecular neuroscience · 2020Article
- From membrane receptors to protein synthesis and actin cytoskeleton: Mechanisms underlying long lasting forms of synaptic plasticity.Seminars in cell & developmental biology · 2019Review
- The Psychiatric Risk Gene NT5C2 Regulates Adenosine Monophosphate-Activated Protein Kinase Signaling and Protein Translation in Human Neural Progenitor Cells.Biological psychiatry · 2019Article
- Activity of translation regulator eukaryotic elongation factor-2 kinase is increased in Parkinson disease brain and its inhibition reduces alpha synuclein toxicity.Acta neuropathologica communications · 2018Article
- Mdm2 mediates FMRP- and Gp1 mGluR-dependent protein translation and neural network activity.Human molecular genetics · 2017Article
- eEF2K/eEF2 Pathway Controls the Excitation/Inhibition Balance and Susceptibility to Epileptic Seizures.Cerebral cortex (New York, N.Y. : 1991) · 2017Article
- Eukaryotic elongation factor 2 kinase as a drug target in cancer, and in cardiovascular and neurodegenerative diseases.Acta pharmacologica Sinica · 2016Review
- Eukaryotic elongation factor 2 kinase regulates the synthesis of microtubule-related proteins in neurons.Journal of neurochemistry · 2016Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The rapid regulation of cell signaling in response to calcium in neurons is essential for real-time processing of large amounts of information in the brain. A vital regulatory component, and one of the most energy-intensive biochemical processes in cells, is the elongation phase of mRNA translation, which is controlled by the Ca(2+)/CaM-dependent elongation factor 2 kinase (eEF2K). However, little is known about the dynamics of eEF2K regulation in neurons despite its established role in learning and synaptic plasticity. To explore eEF2K dynamics in depth, we stimulated synaptic activity in mouse primary cortical neurons. We find that synaptic activity results in a rapid, but transient, increase in eEF2K activity that is regulated by a combination of AMPA and NMDA-type glutamate receptors and the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin complex 1 (mTORC1) pathways. We then used computational modeling to test the hypothesis that considering Ca(2+)-coordinated MEK/ERK, mTORC1, and eEF2k activation is sufficient to describe the observed eEF2K dynamics. Although such a model could partially fit the empirical findings, it also suggested that a crucial positive regulator of eEF2K was also necessary. Through additional modeling and empirical evidence, we demonstrate that AMP kinase (AMPK) is also an important regulator of synaptic activity-driven eEF2K dynamics in neurons. Our combined modeling and experimental findings provide the first evidence that it is necessary to consider the combined interactions of Ca(2+) with MEK/ERK, mTORC1, and AMPK to adequately explain eEF2K regulation in neurons.
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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 Socratic graph.