Reference : Presynaptic inhibition upon CB1 or mGlu2/3 receptor activation requires ERK/MAPK phos...
Scientific journals : Article
Life sciences : Multidisciplinary, general & others
Systems Biomedicine
Presynaptic inhibition upon CB1 or mGlu2/3 receptor activation requires ERK/MAPK phosphorylation of Munc18-1.
Schmitz, Sabine mailto [Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit (VU) and VU Medical Center, Amsterdam, The Netherlands > Department of Functional Genomics and Clinical Genetics]
King, Cillian [> >]
Kortleven, Christian [> >]
Huson, Vincent [> >]
Kroon, Tim [> >]
Kevenaar, Josta T. [> >]
Schut, Desiree [> >]
Saarloos, Ingrid [> >]
Hoetjes, Joost P. [> >]
de Wit, Heidi [> >]
Stiedl, Oliver [> >]
Spijker, Sabine [> >]
Li, Ka Wan [> >]
Mansvelder, Huibert D. [> >]
Smit, August B. [> >]
Cornelisse, Lennart Niels [> >]
Verhage, Matthijs [> >]
Toonen, Ruud F. [> >]
The EMBO journal
Yes (verified by ORBilu)
[en] homeostatic regulation ; presynaptic strength ; synapse
[en] 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 mediatesCB1R- andmGluR2/3-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, preventingERK-dependent Munc18-1 phosphorylation increases synaptic strength.CB1R- andmGluR2/3-induced synaptic inhibition and depolarization-induced suppression of excitation (DSE) are reduced uponERK/MEKpathway inhibition and further reduced whenERK-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.
(c) 2016 The Authors.

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