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

doi:10.1038/ncomms10583

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

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

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.

Original language	English
Article number	10583
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10583
Publication status	Published - Feb 17 2016
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Chemistry(all)
Physics and Astronomy(all)

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10.1038/ncomms10583

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Doi, M., Murai, I., Kunisue, S., Setsu, G., Uchio, N., Tanaka, R., Kobayashi, S., Shimatani, H., Hayashi, H., Chao, H. W., Nakagawa, Y., Takahashi, Y., Hotta, Y., Yasunaga, J. I., Matsuoka, M., Hastings, M. H., Kiyonari, H., & Okamura, H. (2016). Gpr176 is a Gz-linked orphan G-protein-coupled receptor that sets the pace of circadian behaviour. Nature Communications, 7, [10583]. https://doi.org/10.1038/ncomms10583

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.

In: Nature Communications, Vol. 7, 10583, 17.02.2016.

Research output: Contribution to journal › Article › peer-review

Doi, M, Murai, I, Kunisue, S, Setsu, G, Uchio, N, Tanaka, R, Kobayashi, S, Shimatani, H, Hayashi, H, Chao, HW, Nakagawa, Y, Takahashi, Y, Hotta, Y, Yasunaga, JI, Matsuoka, M, Hastings, MH, Kiyonari, H & Okamura, H 2016, 'Gpr176 is a Gz-linked orphan G-protein-coupled receptor that sets the pace of circadian behaviour', Nature Communications, vol. 7, 10583. https://doi.org/10.1038/ncomms10583

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. / Gpr176 is a Gz-linked orphan G-protein-coupled receptor that sets the pace of circadian behaviour. In: Nature Communications. 2016 ; Vol. 7.

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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.",

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AU - Matsuoka, Masao

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