Identification and characterization of a potential drug target regulating the pace of the central circadian clock in the brain

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293013
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Kyoto University
• Principal Investigator: Doi Masao 京都大学, 薬学研究科(研究院), 准教授 (20432578)
• Co-Investigator(Renkei-kenkyūsha): OKAMURA Hitoshi 京都大学, 大学院薬学研究科, 教授 (60158813) ; Jean-Michel Fustin 京都大学, 大学院薬学研究科, 特定講師 (50711818) ; KOBAYASHI Takuya 京都大学, 医学部, 准教授 (20311730)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: G蛋白質共役型受容体 / 体内時計 / オーファン受容体 / 視交叉上核

Outline of Final Research Achievements

The suprachiasmatic nucleus (SCN), the brain’s circadian pacemaker, governs daily rhythms in behavior and physiology. Here we identified and characterized Gpr176 as an SCN-enriched orphan G-protein coupled receptor (GPCR) that sets the pace of the central clock（Doi et al, Nat Commun 2016）. Interestingly, even in the absence of known ligand, Gpr176 has an agonist-independent basal activity to reduce cAMP signaling. A unique cAMP-repressing G-protein subclass Gz is required for the activity of Gpr176. The discovery of the functional orphan GPCR with a novel mode of action within the SCN would be of help to understand the mechanism that underpins the SCN and thereby facilitate searching for a potential specific drug target to modulate the central clock.

Free Research Field

神経科学・内分泌学・時間生物学