RT Journal Article T1 The metabotropic glutamate receptor mGlu7 activates phospholipase C, translocates munc-13-1 protein, and potentiates glutamate release at cerebrocortical nerve terminals A1 Martín Herranz, Ricardo A1 Durroux, Thierry A1 Ciruela, Francisco A1 Sánchez-Prieto Borja, José A1 Pin, Jean-Philippe A1 Torres Molina, Magdalena Isabel AB At synaptic boutons, metabotropic glutamate receptor 7 (mGlu7 receptor) serves as an autoreceptor, inhibiting glutamate release. In this response, mGlu7 receptor triggers pertussis toxin-sensitive G protein activation, reducing presynaptic Ca2+ influx and the subsequent depolarization evoked release. Here we report that receptor coupling to signaling pathways that potentiate release can be seen following prolonged exposure of nerve terminals to the agonist L-(+)-phosphonobutyrate, L-AP4. This novel mGlu7 receptor response involves an increase in the release induced by the Ca2+ ionophore ionomycin, suggesting a mechanism that is independent of Ca 2+ channel activity, but dependent on the downstream exocytotic release machinery. The mGlu7 receptor-mediated potentiation resists exposure to pertussis toxin, but is dependent on phospholipase C, and increased phosphatidylinositol (4,5)-bisphosphate hydrolysis. Furthermore, the potentiation of release does not depend on protein kinase C, although it is blocked by the diacylglycerol-binding site antagonist calphostin C. We also found that activation of mGlu7 receptors translocate the active zone protein essential for synaptic vesicle priming, munc13-1, from soluble to particulate fractions. We propose that the mGlu7 receptor can facilitate or inhibit glutamate release through multiple pathways, thereby exerting homeostatic control of presynaptic function. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. PB Elsevier SN 0021-9258 YR 2010 FD 2010 LK https://hdl.handle.net/20.500.14352/98022 UL https://hdl.handle.net/20.500.14352/98022 LA eng NO Martín, R., Durroux, T., Ciruela, F., Torres, M., Pin, J. P., & Sánchez-Prieto, J. (2010). The metabotropic glutamate receptor mGlu7 activates phospholipase C, translocates munc-13-1 protein, and potentiates glutamate release at cerebrocortical nerve terminals. The Journal of biological chemistry, 285(23), 17907–17917. https://doi.org/10.1074/jbc.M109.080838 DS Docta Complutense RD 12 abr 2025