Modulation of Hippocampal Network Oscillation by PICK1-Dependent Cell Surface Expression of mGlu3 Receptors
| Autor: | Benoît Girard, Jeanne Ster, Pola Tuduri, Maxime Thouaye, Enora Moutin, Nathalie Bouquier, Julie Perroy, Federica Bertaso |
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| Přispěvatelé: | Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), European Project: 646788,H2020,ERC-2014-CoG,VERTICAL CITY(2015), Guerineau, Nathalie C., Versatility of scaffold complexes in vivo to control synaptic plasticity - VERTICAL CITY - - H20202015-06-01 - 2020-05-31 - 646788 - VALID |
| Rok vydání: | 2022 |
| Předmět: |
Male
[SDV]Life Sciences [q-bio] Cell PDZ domain PDZ Domains Hippocampal formation Receptors Metabotropic Glutamate Non-rapid eye movement sleep Hippocampus Cell membrane Glutamatergic Mice medicine Animals [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Receptor Research Articles Adaptor Proteins Signal Transducing Chemistry General Neuroscience Cell Membrane Cell biology [SDV] Life Sciences [q-bio] medicine.anatomical_structure [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] PICK1 Carrier Proteins |
| Zdroj: | J Neurosci Journal of Neuroscience Journal of Neuroscience, 2022, 42 (47), pp.8897-8911. ⟨10.1523/JNEUROSCI.0063-22.2022⟩ |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/JNEUROSCI.0063-22.2022⟩ |
| Popis: | Metabotropic glutamate receptor Type 3 (mGlu3) controls the sleep/wake architecture, which plays a role in the glutamatergic pathophysiology of schizophrenia. Interestingly, mGlu3 receptor expression is decreased in the brain of schizophrenic patients. However, little is known about the molecular mechanisms regulating mGlu3 receptors at the cell membrane. Subcellular receptor localization is strongly dependent on protein–protein interactions. Here we show that mGlu3 interacts with PICK1 and that this scaffolding protein is important for mGlu3 surface expression and function in hippocampal primary cultures. Disruption of their interaction via an mGlu3 C-terminal mimicking peptide or an inhibitor of the PDZ domain of PICK1 altered the functional expression of mGlu3 receptors in neurons. We next investigated the impact of disrupting the mGlu3-PICK1 interaction on hippocampal theta oscillationsin vitroandin vivoin WT male mice. We found a decreased frequency of theta oscillations in organotypic hippocampal slices, similar to what was previously observed in mGlu3 KO mice. In addition, hippocampal theta power was reduced during rapid eye movement sleep, non-rapid eye movement (NREM) sleep, and wake states after intraventricular administration of the mGlu3 C-terminal mimicking peptide. Targeting the mGlu3-PICK1 complex could thus be relevant to the pathophysiology of schizophrenia.SIGNIFICANCE STATEMENTDysregulation of the glutamatergic system might play a role in the pathophysiology of schizophrenia. Metabotropic glutamate receptors Type 3 (mGlu3) have been proposed as potential targets for schizophrenia. Understanding the molecular mechanisms regulating mGlu3 receptor at the cell membrane is critical toward comprehending how their dysfunction contributes to the pathogenesis of schizophrenia. Here we describe that the binding of the signaling and scaffolding protein PICK1 to mGlu3 receptors is important for their localization and physiological functions. The identification of new proteins that associate specifically to mGlu3 receptors will advance our understanding of the regulatory mechanisms associated with their targeting and function and ultimately might provide new therapeutic strategies to counter these psychiatric conditions. |
| Databáze: | OpenAIRE |
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