Gpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock

Abstract Gpr19 encodes an evolutionarily conserved orphan G-protein-coupled receptor (GPCR) with currently no established physiological role in vivo. We characterized Gpr19 expression in the suprachiasmatic nucleus (SCN), the locus of the master circadian clock in the brain, and determined its role...

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Autores principales:	Yoshiaki Yamaguchi, Iori Murai, Kaoru Goto, Shotaro Doi, Huihua Zhou, Genzui Setsu, Hiroyuki Shimatani, Hitoshi Okamura, Takahito Miyake, Masao Doi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fa41915671cb49aa8c6c451ead7970fe
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spelling	oai:doaj.org-article:fa41915671cb49aa8c6c451ead7970fe2021-11-21T12:24:33ZGpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock10.1038/s41598-021-01764-82045-2322https://doaj.org/article/fa41915671cb49aa8c6c451ead7970fe2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01764-8https://doaj.org/toc/2045-2322Abstract Gpr19 encodes an evolutionarily conserved orphan G-protein-coupled receptor (GPCR) with currently no established physiological role in vivo. We characterized Gpr19 expression in the suprachiasmatic nucleus (SCN), the locus of the master circadian clock in the brain, and determined its role in the context of the circadian rhythm regulation. We found that Gpr19 is mainly expressed in the dorsal part of the SCN, with its expression fluctuating in a circadian fashion. A conserved cAMP-responsive element in the Gpr19 promoter was able to produce circadian transcription in the SCN. Gpr19 −/− mice exhibited a prolonged circadian period and a delayed initiation of daily locomotor activity. Gpr19 deficiency caused the downregulation of several genes that normally peak during the night, including Bmal1 and Gpr176. In response to light exposure at night, Gpr19 −/− mice had a reduced capacity for light-induced phase-delays, but not for phase-advances. This defect was accompanied by reduced response of c-Fos expression in the dorsal region of the SCN, while apparently normal in the ventral area of the SCN, in Gpr19 −/− mice. Thus, our data demonstrate that Gpr19 is an SCN-enriched orphan GPCR with a distinct role in circadian regulation and may provide a potential target option for modulating the circadian clock.Yoshiaki YamaguchiIori MuraiKaoru GotoShotaro DoiHuihua ZhouGenzui SetsuHiroyuki ShimataniHitoshi OkamuraTakahito MiyakeMasao DoiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yoshiaki Yamaguchi Iori Murai Kaoru Goto Shotaro Doi Huihua Zhou Genzui Setsu Hiroyuki Shimatani Hitoshi Okamura Takahito Miyake Masao Doi Gpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock
description	Abstract Gpr19 encodes an evolutionarily conserved orphan G-protein-coupled receptor (GPCR) with currently no established physiological role in vivo. We characterized Gpr19 expression in the suprachiasmatic nucleus (SCN), the locus of the master circadian clock in the brain, and determined its role in the context of the circadian rhythm regulation. We found that Gpr19 is mainly expressed in the dorsal part of the SCN, with its expression fluctuating in a circadian fashion. A conserved cAMP-responsive element in the Gpr19 promoter was able to produce circadian transcription in the SCN. Gpr19 −/− mice exhibited a prolonged circadian period and a delayed initiation of daily locomotor activity. Gpr19 deficiency caused the downregulation of several genes that normally peak during the night, including Bmal1 and Gpr176. In response to light exposure at night, Gpr19 −/− mice had a reduced capacity for light-induced phase-delays, but not for phase-advances. This defect was accompanied by reduced response of c-Fos expression in the dorsal region of the SCN, while apparently normal in the ventral area of the SCN, in Gpr19 −/− mice. Thus, our data demonstrate that Gpr19 is an SCN-enriched orphan GPCR with a distinct role in circadian regulation and may provide a potential target option for modulating the circadian clock.
format	article
author	Yoshiaki Yamaguchi Iori Murai Kaoru Goto Shotaro Doi Huihua Zhou Genzui Setsu Hiroyuki Shimatani Hitoshi Okamura Takahito Miyake Masao Doi
author_facet	Yoshiaki Yamaguchi Iori Murai Kaoru Goto Shotaro Doi Huihua Zhou Genzui Setsu Hiroyuki Shimatani Hitoshi Okamura Takahito Miyake Masao Doi
author_sort	Yoshiaki Yamaguchi
title	Gpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock
title_short	Gpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock
title_full	Gpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock
title_fullStr	Gpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock
title_full_unstemmed	Gpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock
title_sort	gpr19 is a circadian clock-controlled orphan gpcr with a role in modulating free-running period and light resetting capacity of the circadian clock
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fa41915671cb49aa8c6c451ead7970fe
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Gpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock

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