201. Ligand-binding and -scavenging of the chemerin receptor GPR1.
- Author
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Fischer, Tobias F., Czerniak, Anne S., Weiß, Tina, Schoeder, Clara T., Wolf, Philipp, Seitz, Oliver, Meiler, Jens, and Beck-Sickinger, Annette G.
- Subjects
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CHEMERIN , *G protein coupled receptors , *DENDRITIC cells , *ARRESTINS , *NATURAL immunity , *HAND signals - Abstract
Tight regulation of cytokines is essential for the initiation and resolution of inflammation. Chemerin, a mediator of innate immunity, mainly acts on chemokine-like receptor 1 (CMKLR1) to induce the migration of macrophages and dendritic cells. The role of the second chemerin receptor, G protein-coupled receptor 1 (GPR1), is still unclear. Here we demonstrate that GPR1 shows ligand-induced arrestin3 recruitment and internalization. The chemerin C-terminus triggers this activation by folding into a loop structure, binding to aromatic residues in the extracellular loops of GPR1. While this overall binding mode is shared between GPR1 and CMKLR1, differences in their respective extracellular loop 2 allowed for the design of the first GPR1-selective peptide. However, our results suggest that ligand-induced arrestin recruitment is not the only mode of action of GPR1. This receptor also displays constitutive internalization, which allows GPR1 to internalize inactive peptides efficiently by an activation-independent pathway. Our results demonstrate that GPR1 takes a dual role in regulating chemerin activity: as a signaling receptor for arrestin-based signaling on one hand, and as a scavenging receptor with broader ligand specificity on the other. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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