mGlu1 receptor canonical signaling pathway contributes to the opening of the orphan GluD2 receptor.
The orphan Glutamate receptor Delta2 (GluD2) intrinsic ion channel activity is indirectly triggered by glutamate through stimulation of the metabotropic glutamate receptor 1 (mGlu1), in cerebellar Purkinje cells. However, the mechanisms of GluD2 ion channel opening are entirely unknown. In this work, we investigated the signaling pathways underlying the mGlu1-induced GluD2 current, performing whole-cell voltage-clamp recordings from mGlu1 and GluD2 transfected HEK293 cells. We show that the activation of GluD2 channels via DHPG-induced mGlu1 stimulation is Gαq-dependent. Moreover, inhibition of the downstream components of the mGlu1 canonical signaling pathway PLC and PKC with U73122 and GF109203X, respectively, strongly reduced the DHPG-induced GluD2 current. These results were further confirmed on endogenous receptors at the Parallel Fiber - Purkinje Cell cerebellar synapse, indicating that the opening of the GluD2 channel by mGlu1 receptor mobilizes the canonical Gq-PLC-PKC pathway. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'.
CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, F-34094, France; INSERM, U1191, Montpellier, F-34094, France; Université de Montpellier, UMR-5203, Montpellier, F-34094, France.
Selma
S
Dadak
CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, F-34094, France; INSERM, U1191, Montpellier, F-34094, France; Université de Montpellier, UMR-5203, Montpellier, F-34094, France.
Nathalie
N
Bouquier
CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, F-34094, France; INSERM, U1191, Montpellier, F-34094, France; Université de Montpellier, UMR-5203, Montpellier, F-34094, France.
Elise
E
Goyet
CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, F-34094, France; INSERM, U1191, Montpellier, F-34094, France; Université de Montpellier, UMR-5203, Montpellier, F-34094, France.
Laurent
L
Fagni
CNRS, UMR 8119 Neurophysics and Physiology Laboratory, Université Paris Descartes, Paris, France.
Carole
C
Levenes
CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, F-34094, France; INSERM, U1191, Montpellier, F-34094, France; Université de Montpellier, UMR-5203, Montpellier, F-34094, France. Electronic address: Julie.Perroy@igf.cnrs.fr.
Julie
J
Perroy
D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology; D004963:Estrenes / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D011760:Pyrrolidinones / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D004963:Estrenes; D007211:Indoles; D008301:Maleimides; D011760:Pyrrolidinones; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; C107913:glutamate receptor delta 2; C104077:metabotropic glutamate receptor type 1; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D008734:Methoxyhydroxyphenylglycol; C070515:bisindolylmaleimide I; C010117:3,4-dihydroxyphenylglycol
Cross-talk; GluD2; Glutamate receptors; mGlu1