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Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2

Chemerin is a small chemotactic protein originally identified as the natural ligand of CMKLR1. More recently, two other receptors, GPR1 and CCRL2, have been reported to bind chemerin but their functional relevance remains poorly understood. In this study, we compared the binding and signaling proper...

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Autores principales: De Henau, Olivier, Degroot, Gaetan-Nagim, Imbault, Virginie, Robert, Virginie, De Poorter, Cédric, Mcheik, Saria, Galés, Céline, Parmentier, Marc, Springael, Jean-Yves
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055294/
https://www.ncbi.nlm.nih.gov/pubmed/27716822
http://dx.doi.org/10.1371/journal.pone.0164179
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author De Henau, Olivier
Degroot, Gaetan-Nagim
Imbault, Virginie
Robert, Virginie
De Poorter, Cédric
Mcheik, Saria
Galés, Céline
Parmentier, Marc
Springael, Jean-Yves
author_facet De Henau, Olivier
Degroot, Gaetan-Nagim
Imbault, Virginie
Robert, Virginie
De Poorter, Cédric
Mcheik, Saria
Galés, Céline
Parmentier, Marc
Springael, Jean-Yves
author_sort De Henau, Olivier
collection PubMed
description Chemerin is a small chemotactic protein originally identified as the natural ligand of CMKLR1. More recently, two other receptors, GPR1 and CCRL2, have been reported to bind chemerin but their functional relevance remains poorly understood. In this study, we compared the binding and signaling properties of the three human chemerin receptors and showed differences in mode of chemerin binding and receptor signaling. Chemerin binds to all three receptors with low nanomolar affinities. However, the contribution of the chemerin C-terminus to binding efficiency varies greatly amongst receptors. By using BRET-based biosensors monitoring the activation of various G proteins, we showed that binding of chemerin and the chemerin 9 nonapeptide ((149)YFPGQFAFS(157)) to CMKLR1 activates the three G(αi) subtypes (G(αi1), G(αi2) and G(αi3)) and the two G(αo) isoforms (G(αoa) and G(αob)) with potencies correlated to binding affinities. In contrast, no significant activation of G proteins was detected upon binding of chemerin to GPR1 or CCRL2. Binding of chemerin and the chemerin 9 peptide also induced the recruitment of β-arrestin1 and 2 to CMKLR1 and GPR1, though to various degree, but not to CCRL2. However, the propensity of chemerin 9 to activate β-arrestins relative to chemerin is higher when bound to GPR1. Finally, we showed that binding of chemerin to CMKLR1 and GPR1 promotes also the internalization of the two receptors and the phosphorylation of ERK1/2 MAP kinases, although with a different efficiency, and that phosphorylation of ERK1/2 requires both G(αi/o) and β-arrestin2 activation but not β-arrestin1. Collectively, these data support a model in which each chemerin receptor displays selective signaling properties.
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spelling pubmed-50552942016-10-27 Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2 De Henau, Olivier Degroot, Gaetan-Nagim Imbault, Virginie Robert, Virginie De Poorter, Cédric Mcheik, Saria Galés, Céline Parmentier, Marc Springael, Jean-Yves PLoS One Research Article Chemerin is a small chemotactic protein originally identified as the natural ligand of CMKLR1. More recently, two other receptors, GPR1 and CCRL2, have been reported to bind chemerin but their functional relevance remains poorly understood. In this study, we compared the binding and signaling properties of the three human chemerin receptors and showed differences in mode of chemerin binding and receptor signaling. Chemerin binds to all three receptors with low nanomolar affinities. However, the contribution of the chemerin C-terminus to binding efficiency varies greatly amongst receptors. By using BRET-based biosensors monitoring the activation of various G proteins, we showed that binding of chemerin and the chemerin 9 nonapeptide ((149)YFPGQFAFS(157)) to CMKLR1 activates the three G(αi) subtypes (G(αi1), G(αi2) and G(αi3)) and the two G(αo) isoforms (G(αoa) and G(αob)) with potencies correlated to binding affinities. In contrast, no significant activation of G proteins was detected upon binding of chemerin to GPR1 or CCRL2. Binding of chemerin and the chemerin 9 peptide also induced the recruitment of β-arrestin1 and 2 to CMKLR1 and GPR1, though to various degree, but not to CCRL2. However, the propensity of chemerin 9 to activate β-arrestins relative to chemerin is higher when bound to GPR1. Finally, we showed that binding of chemerin to CMKLR1 and GPR1 promotes also the internalization of the two receptors and the phosphorylation of ERK1/2 MAP kinases, although with a different efficiency, and that phosphorylation of ERK1/2 requires both G(αi/o) and β-arrestin2 activation but not β-arrestin1. Collectively, these data support a model in which each chemerin receptor displays selective signaling properties. Public Library of Science 2016-10-07 /pmc/articles/PMC5055294/ /pubmed/27716822 http://dx.doi.org/10.1371/journal.pone.0164179 Text en © 2016 De Henau et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
De Henau, Olivier
Degroot, Gaetan-Nagim
Imbault, Virginie
Robert, Virginie
De Poorter, Cédric
Mcheik, Saria
Galés, Céline
Parmentier, Marc
Springael, Jean-Yves
Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2
title Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2
title_full Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2
title_fullStr Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2
title_full_unstemmed Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2
title_short Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2
title_sort signaling properties of chemerin receptors cmklr1, gpr1 and ccrl2
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055294/
https://www.ncbi.nlm.nih.gov/pubmed/27716822
http://dx.doi.org/10.1371/journal.pone.0164179
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