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G protein‐coupled receptor‐1 is an active signaling receptor for the adipokine chemerin
Author(s) -
Rourke Jillian L,
Shanmugam Muruganadan,
Sinal Christopher J
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.669.2
Subject(s) - chemerin , adipokine , rhoa , signal transduction , endocrinology , chemistry , medicine , microbiology and biotechnology , receptor , biology , leptin , obesity
BACKGROUND Chemerin, is an adipose‐derived signaling protein (adipokine) that regulates adipocyte differentiation and metabolism through activation of chemokine‐like receptor‐1 (CMKLR1). Chemerin also binds to G protein‐coupled receptor 1 (GPR1), suggesting that this protein may be a second chemerin signaling receptor. OBJECTIVE To investigate differential signaling and expression of chemerin receptors METHODS Receptor signaling and tissue expression were assessed using a panel of in vitro luciferase‐ reporters and quantitative PCR, respectively. RESULTS GPR1 and CMKLR1 exhibit unique expression profiles which converge with the highest levels of each observed in white adipose tissue (WAT). CMKLR1 is highest in lipid‐filled adipocytes, while GPR1 expression predominates in the WAT stromal vascular fraction. Unlike CMKLR1, chemerin activation of GPR1 does not induce MAPK signaling, but does exhibit higher potency for arrestin recruitment. In common, chemerin activation of both CMKLR1 and GPR1 enhances serum‐response factor (SRF) – mediated gene transcription via a RhoA dependent pathway. CONCLUSIONS These results demonstrate that GPR1 is an active chemerin receptor and identify RhoA/SRF as a novel chemerin signaling axis. Differential receptor expression suggests that GPR1 may play a distinct role in chemerin function in WAT. Supported by CIHR & Killam Trusts