期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/ncomms10583
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资金
- Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Takeda Science Foundation
- Kobayashi International Scholarship Foundation
- Senri Life Science Foundation
- Daiichi Sankyo Foundation of Life Science
- Inoue Foundation for Science
- Brain Science Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Kanae Foundation for the Promotion of Medical Science
- Medical Research Council, UK
- Medical Research Council [MC_U105170643] Funding Source: researchfish
- MRC [MC_U105170643] Funding Source: UKRI
- Grants-in-Aid for Scientific Research [15K15416, 15H05933, 15K21744, 15H01843, 26293013] Funding Source: KAKEN
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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