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Title: | The metabotropic glutamate receptor mGlu7 activates phospholipase C, translocates munc-13-1 protein, and potentiates glutamate release at cerebrocortical nerve terminals |
Author: | Martínez Ribas, Ricardo Durroux, Thierry Ciruela Alférez, Francisco Torres, Magdalena Pin, Jean-Philippe Sánchez-Prieto, José |
Keywords: | Àcid glutàmic Teixit nerviós Neurones Fosfolípids Glutamic acid Nerve tissue Neurons Phospholipids |
Issue Date: | 4-Jun-2010 |
Publisher: | American Society for Biochemistry and Molecular Biology |
Abstract: | 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 Ca(2+) 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 Ca(2+) 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1074/jbc.M109.080838 |
It is part of: | Journal of Biological Chemistry, 2010, vol. 285, num. 23, p. 17907-17917 |
URI: | http://hdl.handle.net/2445/177422 |
Related resource: | https://doi.org/10.1074/jbc.M109.080838 |
ISSN: | 0021-9258 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) |
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