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GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis
G protein–coupled receptor 182 (GPR182) has been shown to be expressed in endothelial cells; however, its ligand and physiological role has remained elusive. We found GPR182 to be expressed in microvascular and lymphatic endothelial cells of most organs and to bind with nanomolar affinity the chemok...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092405/ https://www.ncbi.nlm.nih.gov/pubmed/33875597 http://dx.doi.org/10.1073/pnas.2021596118 |
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author | Le Mercier, Alan Bonnavion, Remy Yu, Weijia Alnouri, Mohamad Wessam Ramas, Sophie Zhang, Yang Jäger, Yannick Roquid, Kenneth Anthony Jeong, Hyun-Woo Sivaraj, Kishor Kumar Cho, Haaglim Chen, Xinyi Strilic, Boris Sijmonsma, Tjeerd Adams, Ralf Schroeder, Timm Rieger, Michael A. Offermanns, Stefan |
author_facet | Le Mercier, Alan Bonnavion, Remy Yu, Weijia Alnouri, Mohamad Wessam Ramas, Sophie Zhang, Yang Jäger, Yannick Roquid, Kenneth Anthony Jeong, Hyun-Woo Sivaraj, Kishor Kumar Cho, Haaglim Chen, Xinyi Strilic, Boris Sijmonsma, Tjeerd Adams, Ralf Schroeder, Timm Rieger, Michael A. Offermanns, Stefan |
author_sort | Le Mercier, Alan |
collection | PubMed |
description | G protein–coupled receptor 182 (GPR182) has been shown to be expressed in endothelial cells; however, its ligand and physiological role has remained elusive. We found GPR182 to be expressed in microvascular and lymphatic endothelial cells of most organs and to bind with nanomolar affinity the chemokines CXCL10, CXCL12, and CXCL13. In contrast to conventional chemokine receptors, binding of chemokines to GPR182 did not induce typical downstream signaling processes, including G(q)- and G(i)-mediated signaling or β-arrestin recruitment. GPR182 showed relatively high constitutive activity in regard to β-arrestin recruitment and rapidly internalized in a ligand-independent manner. In constitutive GPR182-deficient mice, as well as after induced endothelium-specific loss of GPR182, we found significant increases in the plasma levels of CXCL10, CXCL12, and CXCL13. Global and induced endothelium-specific GPR182-deficient mice showed a significant decrease in hematopoietic stem cells in the bone marrow as well as increased colony-forming units of hematopoietic progenitors in the blood and the spleen. Our data show that GPR182 is a new atypical chemokine receptor for CXCL10, CXCL12, and CXCL13, which is involved in the regulation of hematopoietic stem cell homeostasis. |
format | Online Article Text |
id | pubmed-8092405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-80924052021-05-12 GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis Le Mercier, Alan Bonnavion, Remy Yu, Weijia Alnouri, Mohamad Wessam Ramas, Sophie Zhang, Yang Jäger, Yannick Roquid, Kenneth Anthony Jeong, Hyun-Woo Sivaraj, Kishor Kumar Cho, Haaglim Chen, Xinyi Strilic, Boris Sijmonsma, Tjeerd Adams, Ralf Schroeder, Timm Rieger, Michael A. Offermanns, Stefan Proc Natl Acad Sci U S A Biological Sciences G protein–coupled receptor 182 (GPR182) has been shown to be expressed in endothelial cells; however, its ligand and physiological role has remained elusive. We found GPR182 to be expressed in microvascular and lymphatic endothelial cells of most organs and to bind with nanomolar affinity the chemokines CXCL10, CXCL12, and CXCL13. In contrast to conventional chemokine receptors, binding of chemokines to GPR182 did not induce typical downstream signaling processes, including G(q)- and G(i)-mediated signaling or β-arrestin recruitment. GPR182 showed relatively high constitutive activity in regard to β-arrestin recruitment and rapidly internalized in a ligand-independent manner. In constitutive GPR182-deficient mice, as well as after induced endothelium-specific loss of GPR182, we found significant increases in the plasma levels of CXCL10, CXCL12, and CXCL13. Global and induced endothelium-specific GPR182-deficient mice showed a significant decrease in hematopoietic stem cells in the bone marrow as well as increased colony-forming units of hematopoietic progenitors in the blood and the spleen. Our data show that GPR182 is a new atypical chemokine receptor for CXCL10, CXCL12, and CXCL13, which is involved in the regulation of hematopoietic stem cell homeostasis. National Academy of Sciences 2021-04-27 2021-04-19 /pmc/articles/PMC8092405/ /pubmed/33875597 http://dx.doi.org/10.1073/pnas.2021596118 Text en Copyright © 2021 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Le Mercier, Alan Bonnavion, Remy Yu, Weijia Alnouri, Mohamad Wessam Ramas, Sophie Zhang, Yang Jäger, Yannick Roquid, Kenneth Anthony Jeong, Hyun-Woo Sivaraj, Kishor Kumar Cho, Haaglim Chen, Xinyi Strilic, Boris Sijmonsma, Tjeerd Adams, Ralf Schroeder, Timm Rieger, Michael A. Offermanns, Stefan GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis |
title | GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis |
title_full | GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis |
title_fullStr | GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis |
title_full_unstemmed | GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis |
title_short | GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis |
title_sort | gpr182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092405/ https://www.ncbi.nlm.nih.gov/pubmed/33875597 http://dx.doi.org/10.1073/pnas.2021596118 |
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