Type 1 metabotropic glutamate receptors (m
            <scp>G</scp>
            lu1) trigger the gating of
            <scp>G</scp>
            lu
            <scp>D</scp>
            2 delta glutamate receptors

Ady, Visou; Perroy, Julie; Tricoire, Ludovic; Piochon, Claire; Dadak, Selma; Chen, Xiaoru; Dusart, Isabelle; Fagni, Laurent; Lambolez, Bertrand; Lévénès, Carole

doi:10.1002/embr.201337371

Cited by 65 publications

(81 citation statements)

References 46 publications

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“…In particular, studies indicate a reciprocal interaction between GluD2 and mGlu1 receptors in the cerebellar Purkinje cells. GluD2 physically associates with mGlu1, PLCg, and TRPC3 channels in Purkinje cells and regulates mGlu1 function (Uemura et al, 2004;Kato et al, 2012), whereas activation of mGlu1 appears to induce gating of GluD2 (Ady et al, 2014). Our data demonstrate that this interaction may extend to GluD1 and mGlu5 in the forebrain, which may serve as a mechanism to regulate excitatory synapses.…”

Section: Discussionmentioning

confidence: 68%

“…In addition, the behavioral and synaptic deficits that we observe in the GluD1 KO, including impaired NMDA receptor subunit switch and impaired pruning, are deficits observed in mouse models with mGlu5 dysfunction (Vanderklish and Edelman, 2002;Xu et al, 2009;Matta et al, 2011;Cruz-Martin et al, 2012). Moreover, a recent study demonstrated ion channel gating of GluD2 when coexpressed with mGlu1 (Ady et al, 2014). Based on this converging evidence, we hypothesized that GluD1 and mGlu5 are part of a common signaling complex, and that mGlu5 signaling will be impaired in GluD1 KO.…”

Section: Introductionmentioning

confidence: 84%

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Glutamate Delta-1 Receptor Regulates Metabotropic Glutamate Receptor 5 Signaling in the Hippocampus

et al. 2016

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The delta family of ionotropic glutamate receptors consists of glutamate delta-1 (GluD1) and glutamate delta-2 receptors. We have previously shown that GluD1 knockout mice exhibit features of developmental delay, including impaired spine pruning and switch in the N-methyl-D-aspartate receptor subunit, which are relevant to autism and other neurodevelopmental disorders. Here, we identified a novel role of GluD1 in regulating metabotropic glutamate receptor 5 (mGlu5) signaling in the hippocampus. Immunohistochemical analysis demonstrated colocalization of mGlu5 with GluD1 punctas in the hippocampus. Additionally, GluD1 protein coimmunoprecipitated with mGlu5 in the hippocampal membrane fraction, as well as when overexpressed in human embryonic kidney 293 cells, demonstrating that GluD1 and mGlu5 may cooperate in a signaling complex. The interaction of mGlu5 with scaffold protein effector Homer, which regulates mechanistic target of rapamycin (mTOR) signaling, was abnormal both under basal conditions and in response to mGlu1/5 agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) in GluD1 knockout mice. The basal levels of phosphorylated mTOR and protein kinase B, the signaling proteins downstream of mGlu5 activation, were higher in GluD1 knockout mice, and no further increase was induced by DHPG. We also observed higher basal protein translation and an absence of DHPG-induced increase in GluD1 knockout mice. In accordance with a role of mGlu5-mediated mTOR signaling in synaptic plasticity, DHPG-induced internalization of surface a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunits was impaired in the GluD1 knockout mice. These results demonstrate that GluD1 interacts with mGlu5, and loss of GluD1 impairs normal mGlu5 signaling potentially by dysregulating coupling to its effector. These studies identify a novel role of the enigmatic GluD1 subunit in hippocampal function.

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 84%

Glutamate Delta-1 Receptor Regulates Metabotropic Glutamate Receptor 5 Signaling in the Hippocampus

et al. 2016

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“…In the past these subunits were considered orphans and not functional but more recent findings indicate that they are indeed functional, by modulating LTD and prepulse inhibition of the acoustic startle response (sensorimotor gating), and their localization is not restricted to the cerebellum but includes cortical and limbic regions as well. 50–54 …”

Section: Central Glutamatergic Activitymentioning

confidence: 99%

Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings

Bell¹,

Hauser²,

McClintick³

et al. 2016

Progress in Molecular Biology and Translational Science

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Herein, we have reviewed the role of glutamate, the major excitatory neurotransmitter in the brain, in a number of neurochemical, -physiological, and -behavioral processes mediating the development of alcohol dependence. The findings discussed include results from both preclinical as well as neuroimaging and postmortem clinical studies. Expression levels for a number of glutamate-associated genes and/or proteins are modulated by alcohol abuse and dependence. These changes in expression include metabotropic receptors and ionotropic receptor subunits as well as different glutamate transporters. Moreover, these changes in gene expression parallel the pharmacologic manipulation of these same receptors and transporters. Some of these gene expression changes may have predated alcohol abuse and dependence because a number of glutamate-associated polymorphisms are related to a genetic predisposition to develop alcohol dependence. Other glutamate-associated polymorphisms are linked to age at the onset of alcohol-dependence and initial level of response/sensitivity to alcohol. Finally, findings of innate and/or ethanol-induced glutamate-associated gene expression differences/changes observed in a genetic animal model of alcoholism, the P rat, are summarized. Overall, the existing literature indicates that changes in glutamate receptors, transporters, enzymes, and scaffolding proteins are crucial for the development of alcohol dependence and there is a substantial genetic component to these effects. This indicates that continued research into the genetic underpinnings of these glutamate-associated effects will provide important novel molecular targets for treating alcohol abuse and dependence.

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“…Kim et al (2003) presented convincing evidence that mGlu 1 can regulate TRPC1 both in heterologous expression systems and in Purkinje cells. However, later studies showed that the Group I mGlu receptor current is reduced by the selective TRPC3 antagonist Pry3 (Ady et al 2014), is absent in TRPC3 KO mice and present in TRPC1 KO mice (Hartmann et al 2008). Together, these data indicate that TRPC3 channels are responsible, at least partially, for the Group I mGlu receptor current at the cerebellar parallel fiber to the Purkinje cell synapse.…”

Section: Trpc Channelsmentioning

confidence: 92%

Control of neuronal excitability by Group I metabotropic glutamate receptors

Amb

Jds

et al. 2017

Biophys Rev

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Metabotropic glutamate (mGlu) receptors couple through G proteins to regulate a large number of cell functions. Eight mGlu receptor isoforms have been cloned and classified into three Groups based on sequence, signal transduction mechanisms and pharmacology. This review will focus on Group I mGlu receptors, comprising the isoforms mGlu 1 and mGlu 5 . Activation of these receptors initiates both G protein-dependent and -independent signal transduction pathways. The G-protein-dependent pathway involves mainly Gα q , which can activate PLCβ, leading initially to the formation of IP 3 and diacylglycerol. IP 3 can release Ca 2+ from cellular stores resulting in activation of Ca 2+ -dependent ion channels. Intracellular Ca 2+ , together with diacylglycerol, activates PKC, which has many protein targets, including ion channels. Thus, activation of the G-protein-dependent pathway affects cellular excitability though several different effectors. In parallel, G protein-independent pathways lead to activation of non-selective cationic currents and metabotropic synaptic currents and potentials. Here, we provide a survey of the membrane transport proteins responsible for these electrical effects of Group I metabotropic glutamate receptors.

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Type 1 metabotropic glutamate receptors (m G lu1) trigger the gating of G lu D 2 delta glutamate receptors

Cited by 65 publications

References 46 publications

Glutamate Delta-1 Receptor Regulates Metabotropic Glutamate Receptor 5 Signaling in the Hippocampus

Glutamate Delta-1 Receptor Regulates Metabotropic Glutamate Receptor 5 Signaling in the Hippocampus

Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings

Control of neuronal excitability by Group I metabotropic glutamate receptors

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