Regulation of Metabotropic Glutamate Receptor 7 (mGluR7) Internalization and Surface Expression by Ser/Thr Protein Phosphatase 1

Suh, Young Ho; Park, Ji Young; Park, Sangwook; Jou, Ilo; Roche, Paul A.; Roche, Katherine W.

doi:10.1074/jbc.m112.439513

Cited by 29 publications

(24 citation statements)

References 45 publications

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“…We, therefore, propose that the increased probability of release coupled with the increased PLD activity may contribute to multiple vesicular release that results in the constant PPR (Chamberland et al, 2014; Christie and Jahr, 2006; Conti and Lisman, 2003; Oertner et al, 2002) observed and establishes a new synaptic homeostasis that is unresponsive to the pharmacological treatments. Alternatively, mGluR internalization due to increased probability of release in FPS LTM may contribute to the unresponsiveness (Bhattacharya et al, 2004; Pelkey et al, 2005; Suh et al, 2013). A third possibility is that of a ligand-independent action (Lorez et al, 2003) involving mGluR7.…”

Section: Discussionmentioning

confidence: 99%

Fear potentiated startle increases phospholipase D (PLD) expression/activity and PLD-linked metabotropic glutamate receptor mediated post-tetanic potentiation in rat amygdala

Krishnan

Scott

Pollandt

et al. 2016

Neurobiology of Learning and Memory

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Long-term memory (LTM) of fear stores activity dependent modifications that include changes in amygdala signaling. Previously, we identified an enhanced probability of release of glutamate mediated signaling to be important in rat fear potentiated startle (FPS), a well-established translational behavioral measure of fear. Here, we investigated short- and long-term synaptic plasticity in FPS involving metabotropic glutamate receptors (mGluRs) and associated downstream proteomic changes in the thalamic-lateral amygdala pathway (Th-LA). Aldolase A, an inhibitor of phospholipase D (PLD), expression was reduced, concurrent with significantly elevated PLD protein expression. Blocking the PLD-mGluR signaling significantly reduced PLD activity. While transmitter release probability increased in FPS, PLD-mGluR agonist and antagonist actions were occluded. In the unpaired group (UNP), blocking the PLD-mGluR increased while activating the receptor decreased transmitter release probability, consistent with decreased synaptic potentials during tetanic stimulation. FPS Post-tetanic potentiation (PTP) immediately following long-term potentiation (LTP) induction was significantly increased. Blocking PLD-mGluR signaling prevented PTP and reduced cumulative PTP probability but not LTP maintenance in both groups. These effects are similar to those mediated through mGluR7, which is co-immunoprecipitated with PLD in FPS. Lastly, blocking mGluR-PLD in the rat amygdala was sufficient to prevent behavioral expression of fear memory. Thus, our study in the Th-LA pathway provides the first evidence for PLD as an important target of mGluR signaling in amygdala fear-associated memory. Importantly, the PLD-mGluR provides a novel therapeutic target for treating maladaptive fear memories in posttraumatic stress and anxiety disorders.

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Section: Discussionmentioning

confidence: 99%

Fear potentiated startle increases phospholipase D (PLD) expression/activity and PLD-linked metabotropic glutamate receptor mediated post-tetanic potentiation in rat amygdala

Krishnan

Scott

Pollandt

et al. 2016

Neurobiology of Learning and Memory

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“…Two events, mGluR7 phosphorylation by PKC and mGluR7 binding to the PDZ domain-containing protein PICK1, lead to increased mGluR7 expression [ 51 ]. mGluR7 expression is also increased by inhibitors of protein phosphatase 1 (PP1), which counteracts the action of PKC on mGluR7 [ 52 ]. Rodent studies suggest that the interaction of mGluR7 and PICK1 is critical to proper neural function, as disruption of the mGluR7a-PICK1 complex is sufficient to induce absence epilepsy-like seizures [ 53 ].…”

Section: Role Of Mglur7 In Synaptic Transmissionmentioning

confidence: 99%

Metabotropic Glutamate Receptor 7: From Synaptic Function to Therapeutic Implications

Palazzo

Marabese²,

Novellis³

et al. 2016

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Metabotropic glutamate receptor 7 (mGluR7) is localized presynaptically at the active zone of neurotransmitter release. Unlike mGluR4 and mGluR8, which share mGluR7’s presynaptic location, mGluR7 shows low affinity for glutamate and is activated only by high glutamate concentrations. Its wide distribution in the central nervous system (CNS) and evolutionary conservation across species suggest that mGluR7 plays a primary role in controlling excitatory synapse function. High mGluR7 expression has been observed in several brain regions that are critical for CNS functioning and are involved in neurological and psychiatric disorder development. Until the recent discovery of selective ligands for mGluR7, techniques to elucidate its role in neural function were limited to the use of knockout mice and gene silencing. Studies using these two techniques have revealed that mGluR7 modulates emotionality, stress and fear responses. N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082) was reported as the first selective mGluR7 allosteric agonist. Pharmacological effects of AMN082 have not completely confirmed the mGluR7-knockout mouse phenotype; this has been attributed to rapid receptor internalization after drug treatment and to the drug’s apparent lack of in vivo selectivity. Therefore, the more recently developed mGluR7 negative allosteric modulators (NAMs) are crucial for understanding mGluR7 function and for exploiting its potential as a target for therapeutic interventions. This review presents the main findings regarding mGluR7’s effect on modulation of synaptic function and its role in normal CNS function and in models of neurologic and psychiatric disorders.

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“…As mentioned above, the phosphorylation of mGluR5 by active PKC could also be inhibited by binding with CaM in a Ca 2+ dependent manner. Recent studies suggest that mGluR interacting protein Siah1 [ 29 ], Norbin [ 92 ] and PICK1 [ 151 ] which work as competitive inhibitors of CaM may be potential therapeutic anti-epileptic and/or anti-epileptogenic targets. It is therefore reasonable to believe that targeting on CaM may produce significant antiepileptic and/ or antiepileptogenic effect.…”

Section: Mglur Interacting Proteins As Therapeutic Targets In the Conmentioning

confidence: 99%

Metabotropic Glutamate Receptors and Interacting Proteins in Epileptogenesis

Qian¹,

Tang

2016

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Neurotransmitter and receptor systems are involved in different neurological and neuropsychological disorders such as Parkinson's disease, depression, Alzheimer’s disease and epilepsy. Recent advances in studies of signal transduction pathways or interacting proteins of neurotransmitter receptor systems suggest that different receptor systems may share the common signal transduction pathways or interacting proteins which may be better therapeutic targets for development of drugs to effectively control brain diseases. In this paper, we reviewed metabotropic glutamate receptors (mGluRs) and their related signal transduction pathways or interacting proteins in status epilepticus and temporal lobe epilepsy, and proposed some novel therapeutical drug targets for controlling epilepsy and epileptogenesis.

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Regulation of Metabotropic Glutamate Receptor 7 (mGluR7) Internalization and Surface Expression by Ser/Thr Protein Phosphatase 1

Cited by 29 publications

References 45 publications

Fear potentiated startle increases phospholipase D (PLD) expression/activity and PLD-linked metabotropic glutamate receptor mediated post-tetanic potentiation in rat amygdala

Fear potentiated startle increases phospholipase D (PLD) expression/activity and PLD-linked metabotropic glutamate receptor mediated post-tetanic potentiation in rat amygdala

Metabotropic Glutamate Receptor 7: From Synaptic Function to Therapeutic Implications

Metabotropic Glutamate Receptors and Interacting Proteins in Epileptogenesis

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