Academic Journal
Heterodimers of serotonin receptor subtypes 2 are driven by 5-HT 2C protomers
| العنوان: | Heterodimers of serotonin receptor subtypes 2 are driven by 5-HT 2C protomers |
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| المؤلفون: | Moutkine, Imane, Quentin, Emily, Guiard, Bruno P., Maroteaux, Luc, Doly, Stephane |
| المساهمون: | Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), ANR-11-LABX-0035,BIOPSY,Laboratoire de Psychiatrie Biologique(2011) |
| المصدر: | ISSN: 0021-9258. |
| بيانات النشر: | HAL CCSD American Society for Biochemistry and Molecular Biology |
| سنة النشر: | 2017 |
| المجموعة: | Université Toulouse III - Paul Sabatier: HAL-UPS |
| مصطلحات موضوعية: | G protein-coupled receptor (GPCR), cell signaling, cell-surface receptor, dimerization, molecular pharmacology, receptor regulation, serotonin, signal transduction, MESH: Animals, MESH: CHO Cells, MESH: Mice, MESH: Protein Multimerization, MESH: Receptors, 5-HT2, MESH: Synaptic Transmission, MESH: COS Cells, MESH: Cercopithecus aethiops, MESH: Cricetulus, MESH: HEK293 Cells, MESH: Humans, MESH: Locus Coeruleus, MESH: Male, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology |
| الوصف: | International audience ; The serotonin receptor subtypes 2 comprise 5-HT2A, 5-HT2B, and 5-HT2C, which are Gαq-coupled receptors and display distinct pharmacological properties. Although co-expressed in some brain regions and involved in various neurological disorders, their functional interactions have not yet been studied. We report that 5-HT2 receptors can form homo- and heterodimers when expressed alone or co-expressed in transfected cells. Co-immunoprecipitation and bioluminescence resonance energy transfer studies confirmed that 5-HT2C receptors interact with either 5-HT2A or 5-HT2B receptors. Although heterodimerization with 5-HT2C receptors does not alter 5-HT2C Gαq-dependent inositol phosphate signaling, 5-HT2A or 5-HT2B receptor-mediated signaling was totally blunted. This feature can be explained by a dominance of 5-HT2C on 5-HT2A and 5-HT2B receptor binding; in 5-HT2C-containing heterodimers, ligands bind and activate the 5-HT2C protomer exclusively. This dominant effect on the associated protomer was also observed in neurons, supporting the physiological relevance of 5-HT2 receptor heterodimerization in vivo Accordingly, exogenous expression of an inactive form of the 5-HT2C receptor in the locus ceruleus is associated with decreased 5-HT2A-dependent noradrenergic transmission. These data demonstrate that 5-HT2 receptors can form functionally asymmetric heterodimers in vitro and in vivo that must be considered when analyzing the physiological or pathophysiological roles of serotonin in tissues where 5-HT2 receptors are co-expressed. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/28258217; hal-01593841; https://hal.science/hal-01593841; https://hal.science/hal-01593841/document; https://hal.science/hal-01593841/file/JBCrev2_LM.pdf; PUBMED: 28258217 |
| DOI: | 10.1074/jbc.M117.779041 |
| الاتاحة: | https://hal.science/hal-01593841 https://hal.science/hal-01593841/document https://hal.science/hal-01593841/file/JBCrev2_LM.pdf https://doi.org/10.1074/jbc.M117.779041 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.46D1EE |
| قاعدة البيانات: | BASE |
| DOI: | 10.1074/jbc.M117.779041 |
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