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

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

72016-02-17 , Nature Publishing Group
体内時計を調節するオーファンGPCRの同定 -生体リズム調整薬の開発に期待-. 京都大学プレスリリース. 2016-02-18.
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.

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