Open AccessGPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis
Author(s) -
Audrey Mercier,
Rémy Bonnavion,
Weijia Yu,
Mohamad Wessam Alnouri,
Sophie Ramas,
Yang Zhang,
Yannick Jäger,
Kenneth Anthony Roquid,
HyunWoo Jeong,
Kishor K. Sivaraj,
Haaglim Cho,
Xinyi Chen,
Boris Strilić,
Tjeerd Sijmonsma,
Ralf H. Adams,
Timm Schroeder,
Michael A. Rieger,
Stefan Offermanns
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2021596118
Subject(s) - cxcl13 , microbiology and biotechnology , biology , cxcl10 , chemokine receptor , haematopoiesis , stem cell , ccl21 , chemokine , cxcl14 , progenitor cell , cxcr4 , endothelial stem cell , hematopoietic stem cell , receptor , biochemistry , in vitro
Significance G protein–coupled receptors (GPCRs) are important regulators of cellular and biological functions and are primary targets of therapeutic drugs. About 100 mammalian GPCRs are still considered orphan receptors because they lack a known endogenous ligand. We report the deorphanization of GPR182, which is expressed in endothelial cells of the microvasculature. We show that GPR182 is an atypical chemokine receptor, which binds CXCL10, 12, and 13. However, binding does not induce downstream signaling. Consistent with a scavenging function of GPR182, mice lacking GPR182 have increased plasma levels of chemokines. In line with the crucial role of CXCL12 in hematopoietic stem cell homeostasis, we found that loss of GPR182 results in increased egress of hematopoietic stem cells from the bone marrow.