Gpr176 is a Gz-linked orphan G-protein-coupled receptor that sets the pace of circadian behaviour

Masao Doi, Iori Murai, Sumihiro Kunisue, Genzui Setsu, Naohiro Uchio, Rina Tanaka, Sakurako Kobayashi, Hiroyuki Shimatani, Hida Hayashi, Hsu Wen Chao, Yuuki Nakagawa, Yukari Takahashi, Yunhong Hotta, Jun Ichirou Yasunaga, Masao Matsuoka, Michael H. Hastings, Hiroshi Kiyonari, Hitoshi Okamura

研究成果: 雜誌貢獻文章同行評審

28 引文 斯高帕斯(Scopus)


G-protein-coupled receptors (GPCRs) participate in a broad range of physiological functions. A priority for fundamental and clinical research, therefore, is to decipher the function of over 140 remaining orphan GPCRs. The suprachiasmatic nucleus (SCN), the brain's circadian pacemaker, governs daily rhythms in behaviour and physiology. Here we launch the SCN orphan GPCR project to (i) search for murine orphan GPCRs with enriched expression in the SCN, (ii) generate mutant animals deficient in candidate GPCRs, and (iii) analyse the impact on circadian rhythms. We thereby identify Gpr176 as an SCN-enriched orphan GPCR that sets the pace of circadian behaviour. Gpr176 is expressed in a circadian manner by SCN neurons, and molecular characterization reveals that it represses cAMP signalling in an agonist-independent manner. Gpr176 acts independently of, and in parallel to, the Vipr2 GPCR, not through the canonical Gi, but via the unique G-protein subclass Gz.
期刊Nature Communications
出版狀態已發佈 - 二月 17 2016

ASJC Scopus subject areas

  • 生物化學、遺傳與分子生物學 (全部)
  • 化學 (全部)
  • 物理與天文學 (全部)


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