Ligand-binding and -scavenging of the chemerin receptor GPR1
Open Access
- 9 July 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cellular and Molecular Life Sciences
- Vol. 78 (17-18), 6265-6281
- https://doi.org/10.1007/s00018-021-03894-8
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. Graphic abstractKeywords
Funding Information
- Deutsche Forschungsgemeinschaft (209933838 – SFB 1052 – C08)
- Universität Leipzig
This publication has 64 references indexed in Scilit:
- Proteolytic Cleavage of Chemerin Protein Is Necessary for Activation to the Active Form, Chem157S, Which Functions as a Signaling Molecule in GlioblastomaOnline Journal of Public Health Informatics, 2011
- Chemerin activates fibroblast-like synoviocytes in patients with rheumatoid arthritisArthritis Research & Therapy, 2011
- Chemerin: at the crossroads of inflammation and obesityTrends in Endocrinology & Metabolism, 2010
- Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide AntagonistsScience, 2010
- Chemerin Is Associated with Metabolic Syndrome Phenotypes in a Mexican-American PopulationJournal of Clinical Endocrinology & Metabolism, 2009
- The human complement fragment receptor, C5L2, is a recycling decoy receptorMolecular Immunology, 2009
- Constitutive Internalization of G Protein-coupled Receptors and G Proteins via Clathrin-independent EndocytosisOnline Journal of Public Health Informatics, 2009
- Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitmentThe Journal of Experimental Medicine, 2008
- Mast cell–expressed orphan receptor CCRL2 binds chemerin and is required for optimal induction of IgE-mediated passive cutaneous anaphylaxisThe Journal of Experimental Medicine, 2008
- The genetic design of signaling cascades to record receptor activationProceedings of the National Academy of Sciences of the United States of America, 2008