mGlu1 receptor canonical signaling pathway contributes to the opening of the orphan GluD2 receptor.

Selma Dadak, Nathalie Bouquier, Elise Goyet, Laurent Fagni, Carole Levenes, Julie Perroy
Neuropharmacology. 2017-03-01; 115: 92-99
DOI: 10.1016/j.neuropharm.2016.06.001

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1. Neuropharmacology. 2017 Mar 15;115:92-99. doi: 10.1016/j.neuropharm.2016.06.001.
Epub 2016 Jun 6.

mGlu1 receptor canonical signaling pathway contributes to the opening of the
orphan GluD2 receptor.

Dadak S(1), Bouquier N(1), Goyet E(1), Fagni L(1), Levenes C(2), Perroy J(3).

Author information:
(1)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.
(2)CNRS, UMR 8119 Neurophysics and Physiology Laboratory, Université Paris
Descartes, Paris, France.
(3)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:
.

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’.

Copyright © 2016 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.neuropharm.2016.06.001
PMID: 27276689 [Indexed for MEDLINE]


Auteurs Bordeaux Neurocampus