气候变化领域集成服务门户(CCPortal): GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis

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DOI	10.1073/pnas.2021596118
	GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis
	Le Mercier A.; Bonnavion R.; Yu W.; Alnouri M.W.; Ramas S.; Zhang Y.; Jäger Y.; Roquid K.A.; Jeong H.-W.; Sivaraj K.K.; Cho H.; Chen X.; Strilic B.; Sijmonsma T.; Adams R.; Schroeder T.; Rieger M.A.; Offermanns S.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	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 Gq- and Gi-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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Chemokine; GPCR; Orphan
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179767
作者单位	Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, 61231, Germany; Department of Medicine, Hematology/Oncology, Goethe University Hospital, Frankfurt, 60590, Germany; Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zurich, Basel, 4058, Switzerland; Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, 48149, Germany; German Cancer Consortium, German Cancer Research Center, Heidelberg, 69120, Germany; Frankfurt Cancer Institute, Frankfurt, 60590, Germany; Cardio-Pulmonary Institute, Frankfurt, 60590, Germany; German Centre for Cardiovascular Research, Rhine-Main site, Frankfurt and Bad Nauheim, 60590, Germany; Centre for Molecular Medicine, Medical Faculty, Goethe University Frankfurt, Frankfurt, 60590, Germany
推荐引用方式 GB/T 7714	Le Mercier A.,Bonnavion R.,Yu W.,et al. GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis[J],2021,118(17).
APA	Le Mercier A..,Bonnavion R..,Yu W..,Alnouri M.W..,Ramas S..,...&Offermanns S..(2021).GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Le Mercier A.,et al."GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).