ArticleThe EMBO journal2016
Presynaptic inhibition upon CB1 or mGlu2/3 receptor activation requires ERK/MAPK phosphorylation of Munc18-1.
Article in The EMBO journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Investigating metabotropic glutamate receptors as molecular targets for next-generation pharmacotherapies for alcohol use disorder.Expert opinion on therapeutic targets · 2026Review
- β-arrestin1 orchestrates endosomal signaling to regulate translational control of circadian light entrainment.Communications biology · 2026Article
- Canonical Cannabinoid Receptors.Current topics in behavioral neurosciences · 2026Review
- mGlu2 Receptors in the Basal Ganglia: A New Frontier in Addiction Therapy.Frontiers in bioscience (Landmark edition) · 2025Review
- Microglia Support Both the Singular Form of LTP Expressed by the Lateral Perforant Path and Episodic Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- CB1 receptor coupling to extracellular regulated kinase via multiple Gαi/o isoforms.Neuroreport · 2025Article
- Synaptic Targets and Cellular Sources of CB1 Cannabinoid Receptor and Vesicular Glutamate Transporter-3 Expressing Nerve Terminals in Relation to GABAergic Neurons in the Human Cerebral Cortex.The European journal of neuroscience · 2025Article
- Astrocytic PAR1 and mGluR2/3 control synaptic glutamate time course at hippocampal CA1 synapses.Glia · 2024Article
- Contributions of site- and sex-specific LTPs to everyday memory.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Molecular Adaptations of BDNF/NT-4 Neurotrophic and Muscarinic Pathways in Ageing Neuromuscular Synapses.International journal of molecular sciences · 2024Article
- Reduced MUNC18-1 Levels, Synaptic Proteome Changes, and Altered Network Activity inBiological psychiatry global open science · 2024Article
- Dynamic Changes in the Endocannabinoid System during the Aging Process: Focus on the Middle-Age Crisis.International journal of molecular sciences · 2022Article
- Persistent sexually dimorphic effects of adolescent THC exposure on hippocampal synaptic plasticity and episodic memory in rodents.Neurobiology of disease · 2022Article
- Endocannabinoid-Mediated Control of Neural Circuit Excitability and Epileptic Seizures.Frontiers in neural circuits · 2021Review
- CBeLife · 2020Article
- Glu-mGluR2/3-ERK Signaling Regulates Apoptosis of Hippocampal Neurons in Diabetic-Depression Model Rats.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling.Cellular and molecular life sciences : CMLS · 2018Review
- Long-Term Plasticity of Neurotransmitter Release: Emerging Mechanisms and Contributions to Brain Function and Disease.Annual review of neuroscience · 2018Review
- Atypical Endocannabinoid Signaling Initiates a New Form of Memory-Related Plasticity at a Cortical Input to Hippocampus.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
- Article
Corrections and comments
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Presynaptic cannabinoid (CB1R) and metabotropic glutamate receptors (mGluR2/3) regulate synaptic strength by inhibiting secretion. Here, we reveal a presynaptic inhibitory pathway activated by extracellular signal-regulated kinase (ERK) that mediates CB1R- and mGluR2/3-induced secretion inhibition. This pathway is triggered by a variety of events, from foot shock-induced stress to intense neuronal activity, and induces phosphorylation of the presynaptic protein Munc18-1. Mimicking constitutive phosphorylation of Munc18-1 results in a drastic decrease in synaptic transmission. ERK-mediated phosphorylation of Munc18-1 ultimately leads to degradation by the ubiquitin-proteasome system. Conversely, preventing ERK-dependent Munc18-1 phosphorylation increases synaptic strength. CB1R- and mGluR2/3-induced synaptic inhibition and depolarization-induced suppression of excitation (DSE) are reduced upon ERK/MEK pathway inhibition and further reduced when ERK-dependent Munc18-1 phosphorylation is blocked. Thus, ERK-dependent Munc18-1 phosphorylation provides a major negative feedback loop to control synaptic strength upon activation of presynaptic receptors and during intense neuronal activity.
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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.