The Atypical Chemerin Receptor GPR1 Displays Different Modes of Interaction with β-Arrestins in Humans and Mice with Important Consequences on Subcellular Localization and Trafficking
Atypical chemokine receptors (ACKRs) have emerged as a subfamily of chemokine receptors regulating the local bioavailability of their ligands through scavenging, concentration, or transport. The biological roles of ACKRs in human physiology and diseases are often studied by using transgenic mouse mo...
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MDPI AG
2022-03-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/6/1037 |
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| author | Gaetan-Nagim Degroot Valentin Lepage Marc Parmentier Jean-Yves Springael |
| author_facet | Gaetan-Nagim Degroot Valentin Lepage Marc Parmentier Jean-Yves Springael |
| author_sort | Gaetan-Nagim Degroot |
| collection | DOAJ |
| description | Atypical chemokine receptors (ACKRs) have emerged as a subfamily of chemokine receptors regulating the local bioavailability of their ligands through scavenging, concentration, or transport. The biological roles of ACKRs in human physiology and diseases are often studied by using transgenic mouse models. However, it is unknown whether mouse and human ACKRs share the same properties. In this study, we compared the properties of the human and mouse atypical chemerin receptor GPR1 and showed that they behave differently regarding their interaction with β-arrestins. Human hGPR1 interacts with β-arrestins as a result of chemerin stimulation, whereas its mouse orthologue mGPR1 displays a strong constitutive interaction with β-arrestins in basal conditions. The constitutive interaction of mGPR1 with β-arrestins is accompanied by a redistribution of the receptor from the plasma membrane to early and recycling endosomes. In addition, β-arrestins appear mandatory for the chemerin-induced internalization of mGPR1, whereas they are dispensable for the trafficking of hGPR1. However, mGPR1 scavenges chemerin and activates MAP kinases ERK1/2 similarly to hGPR1. Finally, we showed that the constitutive interaction of mGPR1 with β-arrestins required different structural constituents, including the receptor C-terminus and arginine 3.50 in the second intracellular loop. Altogether, our results show that sequence variations within cytosolic regions of GPR1 orthologues influence their ability to interact with β-arrestins, with important consequences on GPR1 subcellular distribution and trafficking. |
| first_indexed | 2024-03-09T20:01:15Z |
| format | Article |
| id | doaj.art-b77e8031198747c7a4a13137ec6190f3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:01:15Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b77e8031198747c7a4a13137ec6190f32023-11-24T00:44:59ZengMDPI AGCells2073-44092022-03-01116103710.3390/cells11061037The Atypical Chemerin Receptor GPR1 Displays Different Modes of Interaction with β-Arrestins in Humans and Mice with Important Consequences on Subcellular Localization and TraffickingGaetan-Nagim Degroot0Valentin Lepage1Marc Parmentier2Jean-Yves Springael3Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), 1070 Brussels, BelgiumInstitut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), 1070 Brussels, BelgiumInstitut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), 1070 Brussels, BelgiumInstitut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), 1070 Brussels, BelgiumAtypical chemokine receptors (ACKRs) have emerged as a subfamily of chemokine receptors regulating the local bioavailability of their ligands through scavenging, concentration, or transport. The biological roles of ACKRs in human physiology and diseases are often studied by using transgenic mouse models. However, it is unknown whether mouse and human ACKRs share the same properties. In this study, we compared the properties of the human and mouse atypical chemerin receptor GPR1 and showed that they behave differently regarding their interaction with β-arrestins. Human hGPR1 interacts with β-arrestins as a result of chemerin stimulation, whereas its mouse orthologue mGPR1 displays a strong constitutive interaction with β-arrestins in basal conditions. The constitutive interaction of mGPR1 with β-arrestins is accompanied by a redistribution of the receptor from the plasma membrane to early and recycling endosomes. In addition, β-arrestins appear mandatory for the chemerin-induced internalization of mGPR1, whereas they are dispensable for the trafficking of hGPR1. However, mGPR1 scavenges chemerin and activates MAP kinases ERK1/2 similarly to hGPR1. Finally, we showed that the constitutive interaction of mGPR1 with β-arrestins required different structural constituents, including the receptor C-terminus and arginine 3.50 in the second intracellular loop. Altogether, our results show that sequence variations within cytosolic regions of GPR1 orthologues influence their ability to interact with β-arrestins, with important consequences on GPR1 subcellular distribution and trafficking.https://www.mdpi.com/2073-4409/11/6/1037chemerinACKRGPR1β-arrestinssignaling |
| spellingShingle | Gaetan-Nagim Degroot Valentin Lepage Marc Parmentier Jean-Yves Springael The Atypical Chemerin Receptor GPR1 Displays Different Modes of Interaction with β-Arrestins in Humans and Mice with Important Consequences on Subcellular Localization and Trafficking Cells chemerin ACKR GPR1 β-arrestins signaling |
| title | The Atypical Chemerin Receptor GPR1 Displays Different Modes of Interaction with β-Arrestins in Humans and Mice with Important Consequences on Subcellular Localization and Trafficking |
| title_full | The Atypical Chemerin Receptor GPR1 Displays Different Modes of Interaction with β-Arrestins in Humans and Mice with Important Consequences on Subcellular Localization and Trafficking |
| title_fullStr | The Atypical Chemerin Receptor GPR1 Displays Different Modes of Interaction with β-Arrestins in Humans and Mice with Important Consequences on Subcellular Localization and Trafficking |
| title_full_unstemmed | The Atypical Chemerin Receptor GPR1 Displays Different Modes of Interaction with β-Arrestins in Humans and Mice with Important Consequences on Subcellular Localization and Trafficking |
| title_short | The Atypical Chemerin Receptor GPR1 Displays Different Modes of Interaction with β-Arrestins in Humans and Mice with Important Consequences on Subcellular Localization and Trafficking |
| title_sort | atypical chemerin receptor gpr1 displays different modes of interaction with β arrestins in humans and mice with important consequences on subcellular localization and trafficking |
| topic | chemerin ACKR GPR1 β-arrestins signaling |
| url | https://www.mdpi.com/2073-4409/11/6/1037 |
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