Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons
Abstract G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins and are important drug targets. The discovery of drugs targeting these receptors and their G protein signaling properties are based on assays mainly performed with modified receptors expressed in heterolo...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46177-z |
| _version_ | 1797273963823366144 |
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| author | Chanjuan Xu Yiwei Zhou Yuxuan Liu Li Lin Peng Liu Xiaomei Wang Zhengyuan Xu Jean-Philippe Pin Philippe Rondard Jianfeng Liu |
| author_facet | Chanjuan Xu Yiwei Zhou Yuxuan Liu Li Lin Peng Liu Xiaomei Wang Zhengyuan Xu Jean-Philippe Pin Philippe Rondard Jianfeng Liu |
| author_sort | Chanjuan Xu |
| collection | DOAJ |
| description | Abstract G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins and are important drug targets. The discovery of drugs targeting these receptors and their G protein signaling properties are based on assays mainly performed with modified receptors expressed in heterologous cells. However, GPCR responses may differ in their native environment. Here, by using highly sensitive Gi/o sensors, we reveal specific properties of Gi/o protein-mediated responses triggered by GABAB, α2 adrenergic and cannabinoid CB1 receptors in primary neurons, different from those in heterologous cells. These include different profiles in the Gi/o protein subtypes-mediated responses, and differences in the potencies of some ligands even at similar receptor expression levels. Altogether, our results show the importance of using biosensors compatible with primary cells for evaluating the activities of endogenous GPCRs in their native environment. |
| first_indexed | 2024-03-07T14:51:42Z |
| format | Article |
| id | doaj.art-85a6b4f2dd3241fba99b3d3521990c96 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:51:42Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-85a6b4f2dd3241fba99b3d3521990c962024-03-05T19:41:13ZengNature PortfolioNature Communications2041-17232024-03-0115111410.1038/s41467-024-46177-zSpecific pharmacological and Gi/o protein responses of some native GPCRs in neuronsChanjuan Xu0Yiwei Zhou1Yuxuan Liu2Li Lin3Peng Liu4Xiaomei Wang5Zhengyuan Xu6Jean-Philippe Pin7Philippe Rondard8Jianfeng Liu9Cellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and TechnologyCellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and TechnologyCellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and TechnologyCellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and TechnologyCellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and TechnologyCellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and TechnologyCellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and TechnologyInstitut de Génomique Fonctionnelle (IGF), Université de Montpellier, CNRS, INSERMInstitut de Génomique Fonctionnelle (IGF), Université de Montpellier, CNRS, INSERMCellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and TechnologyAbstract G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins and are important drug targets. The discovery of drugs targeting these receptors and their G protein signaling properties are based on assays mainly performed with modified receptors expressed in heterologous cells. However, GPCR responses may differ in their native environment. Here, by using highly sensitive Gi/o sensors, we reveal specific properties of Gi/o protein-mediated responses triggered by GABAB, α2 adrenergic and cannabinoid CB1 receptors in primary neurons, different from those in heterologous cells. These include different profiles in the Gi/o protein subtypes-mediated responses, and differences in the potencies of some ligands even at similar receptor expression levels. Altogether, our results show the importance of using biosensors compatible with primary cells for evaluating the activities of endogenous GPCRs in their native environment.https://doi.org/10.1038/s41467-024-46177-z |
| spellingShingle | Chanjuan Xu Yiwei Zhou Yuxuan Liu Li Lin Peng Liu Xiaomei Wang Zhengyuan Xu Jean-Philippe Pin Philippe Rondard Jianfeng Liu Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons Nature Communications |
| title | Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons |
| title_full | Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons |
| title_fullStr | Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons |
| title_full_unstemmed | Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons |
| title_short | Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons |
| title_sort | specific pharmacological and gi o protein responses of some native gpcrs in neurons |
| url | https://doi.org/10.1038/s41467-024-46177-z |
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