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 | |
| Publication status | Published - Feb 17 2016 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Chemistry(all)
- Physics and Astronomy(all)
Cite this
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
}
TY - JOUR
T1 - Gpr176 is a Gz-linked orphan G-protein-coupled receptor that sets the pace of circadian behaviour
AU - Doi, Masao
AU - Murai, Iori
AU - Kunisue, Sumihiro
AU - Setsu, Genzui
AU - Uchio, Naohiro
AU - Tanaka, Rina
AU - Kobayashi, Sakurako
AU - Shimatani, Hiroyuki
AU - Hayashi, Hida
AU - Chao, Hsu Wen
AU - Nakagawa, Yuuki
AU - Takahashi, Yukari
AU - Hotta, Yunhong
AU - Yasunaga, Jun Ichirou
AU - Matsuoka, Masao
AU - Hastings, Michael H.
AU - Kiyonari, Hiroshi
AU - Okamura, Hitoshi
PY - 2016/2/17
Y1 - 2016/2/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84958567860&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84958567860&partnerID=8YFLogxK
U2 - 10.1038/ncomms10583
DO - 10.1038/ncomms10583
M3 - Article
AN - SCOPUS:84958567860
VL - 7
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 10583
ER -