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 and Hitoshi Okamura ()
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Masao Doi: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku
Iori Murai: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku
Sumihiro Kunisue: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku
Genzui Setsu: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku
Naohiro Uchio: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku
Rina Tanaka: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku
Sakurako Kobayashi: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku
Hiroyuki Shimatani: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku
Hida Hayashi: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku
Hsu-Wen Chao: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku
Yuuki Nakagawa: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku
Yukari Takahashi: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku
Yunhong Hotta: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku
Jun-ichirou Yasunaga: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Sakyo-ku
Masao Matsuoka: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Sakyo-ku
Michael H. Hastings: Medical Research Council Laboratory of Molecular Biology
Hiroshi Kiyonari: Animal Resource Development Unit and Genetic Engineering Team, RIKEN Center for Life Science Technologies
Hitoshi Okamura: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms10583

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