Heterodimerization of Mu Opioid Receptor Protomer with Dopamine D<sub>2</sub> Receptor Modulates Agonist-Induced Internalization of Mu Opioid Receptor
The interplay between the dopamine (DA) and opioid systems in the brain is known to modulate the additive effects of substances of abuse. On one hand, opioids serve mankind by their analgesic properties, which are mediated via the mu opioid receptor (MOR), a Class A G protein-coupled receptor (GPCR)...
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MDPI AG
2019-08-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/9/8/368 |
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| author | Lakshmi Vasudevan Dasiel O. Borroto-Escuela Jelle Huysentruyt Kjell Fuxe Deepak K. Saini Christophe Stove |
| author_facet | Lakshmi Vasudevan Dasiel O. Borroto-Escuela Jelle Huysentruyt Kjell Fuxe Deepak K. Saini Christophe Stove |
| author_sort | Lakshmi Vasudevan |
| collection | DOAJ |
| description | The interplay between the dopamine (DA) and opioid systems in the brain is known to modulate the additive effects of substances of abuse. On one hand, opioids serve mankind by their analgesic properties, which are mediated via the mu opioid receptor (MOR), a Class A G protein-coupled receptor (GPCR), but on the other hand, they pose a potential threat by causing undesired side effects such as tolerance and dependence, for which the exact molecular mechanism is still unknown. Using human embryonic kidney 293T (HEK 293T) and HeLa cells transfected with MOR and the dopamine D<sub>2</sub> receptor (D<sub>2</sub>R), we demonstrate that these receptors heterodimerize, using an array of biochemical and biophysical techniques such as coimmunoprecipitation (co-IP), bioluminescence resonance energy transfer (BRET<sup>1</sup>), Fӧrster resonance energy transfer (FRET), and functional complementation of a split luciferase. Furthermore, live cell imaging revealed that D<sub>2L</sub>R, when coexpressed with MOR, slowed down internalization of MOR, following activation with the MOR agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO). |
| first_indexed | 2024-12-12T22:26:23Z |
| format | Article |
| id | doaj.art-e0f3a6cfb34046c694cd276282e732b9 |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-12T22:26:23Z |
| publishDate | 2019-08-01 |
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| series | Biomolecules |
| spelling | doaj.art-e0f3a6cfb34046c694cd276282e732b92022-12-22T00:09:45ZengMDPI AGBiomolecules2218-273X2019-08-019836810.3390/biom9080368biom9080368Heterodimerization of Mu Opioid Receptor Protomer with Dopamine D<sub>2</sub> Receptor Modulates Agonist-Induced Internalization of Mu Opioid ReceptorLakshmi Vasudevan0Dasiel O. Borroto-Escuela1Jelle Huysentruyt2Kjell Fuxe3Deepak K. Saini4Christophe Stove5Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, BelgiumDepartment of Neuroscience, Karolinska Institutet, 17177 Stockholm, SwedenLaboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, BelgiumDepartment of Neuroscience, Karolinska Institutet, 17177 Stockholm, SwedenDepartment of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, IndiaLaboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, BelgiumThe interplay between the dopamine (DA) and opioid systems in the brain is known to modulate the additive effects of substances of abuse. On one hand, opioids serve mankind by their analgesic properties, which are mediated via the mu opioid receptor (MOR), a Class A G protein-coupled receptor (GPCR), but on the other hand, they pose a potential threat by causing undesired side effects such as tolerance and dependence, for which the exact molecular mechanism is still unknown. Using human embryonic kidney 293T (HEK 293T) and HeLa cells transfected with MOR and the dopamine D<sub>2</sub> receptor (D<sub>2</sub>R), we demonstrate that these receptors heterodimerize, using an array of biochemical and biophysical techniques such as coimmunoprecipitation (co-IP), bioluminescence resonance energy transfer (BRET<sup>1</sup>), Fӧrster resonance energy transfer (FRET), and functional complementation of a split luciferase. Furthermore, live cell imaging revealed that D<sub>2L</sub>R, when coexpressed with MOR, slowed down internalization of MOR, following activation with the MOR agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO).https://www.mdpi.com/2218-273X/9/8/368G protein-coupled receptorheterodimerizationmu opioid receptordopamine D<sub>2</sub> receptor |
| spellingShingle | Lakshmi Vasudevan Dasiel O. Borroto-Escuela Jelle Huysentruyt Kjell Fuxe Deepak K. Saini Christophe Stove Heterodimerization of Mu Opioid Receptor Protomer with Dopamine D<sub>2</sub> Receptor Modulates Agonist-Induced Internalization of Mu Opioid Receptor Biomolecules G protein-coupled receptor heterodimerization mu opioid receptor dopamine D<sub>2</sub> receptor |
| title | Heterodimerization of Mu Opioid Receptor Protomer with Dopamine D<sub>2</sub> Receptor Modulates Agonist-Induced Internalization of Mu Opioid Receptor |
| title_full | Heterodimerization of Mu Opioid Receptor Protomer with Dopamine D<sub>2</sub> Receptor Modulates Agonist-Induced Internalization of Mu Opioid Receptor |
| title_fullStr | Heterodimerization of Mu Opioid Receptor Protomer with Dopamine D<sub>2</sub> Receptor Modulates Agonist-Induced Internalization of Mu Opioid Receptor |
| title_full_unstemmed | Heterodimerization of Mu Opioid Receptor Protomer with Dopamine D<sub>2</sub> Receptor Modulates Agonist-Induced Internalization of Mu Opioid Receptor |
| title_short | Heterodimerization of Mu Opioid Receptor Protomer with Dopamine D<sub>2</sub> Receptor Modulates Agonist-Induced Internalization of Mu Opioid Receptor |
| title_sort | heterodimerization of mu opioid receptor protomer with dopamine d sub 2 sub receptor modulates agonist induced internalization of mu opioid receptor |
| topic | G protein-coupled receptor heterodimerization mu opioid receptor dopamine D<sub>2</sub> receptor |
| url | https://www.mdpi.com/2218-273X/9/8/368 |
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