CBBM Lecture "A new class of Gz-linked orphan GPCR in the brain’s central clock"

by Prof. Masao Doi,

Department of Systems Biology,

Graduate School of Pharmaceutical Sciences,

Kyoto University

will take place on Tuesday, June 14, 2016 from 17:15 to 18:15 hours in CBBM, EG, Room 50/51.

Host: Prof. Henrik Oster
Department of Internal Medicine I
Universität zu Lübeck


A set of circadian pacemaker neurons that governs daily rhythms in behaviour and physiology resides in the suprachiasmatic nucleus (SCN) in the brain. Malfunction of the circadian clock has been linked to the pathogenesis of a wide variety of diseases (Doi et al, Nat Med 2010), and development of drugs that target the central clock remains an unfulfilled opportunity for the circadian pharmacology. G protein-coupled receptors (GPCRs) represent an enormously important class of drug targets. However, there are still more than 140 orphan GPCRs whose cognate ligands are not known, and deciphering their physiological function remains a priority for both clinical and fundamental research. In a previous report, we surveyed all known orphan GPCRs expressed in the SCN, and identified Gpr176 (Doi et al, Nat Commun 2016). Gpr176 is a unique orphan GPCR that can set the pace of circadian behavior. Gpr176 is expressed mainly in the brain, with prominent expression in the SCN, and its protein abundance fluctuates in a circadian fashion. Molecular characterization further revealed that this orphan receptor has an agonist-independent basal activity to repress cAMP production. Notably, the unique G-protein subclass Gz, but not the canonical Gi, is required for the activity of Gpr176. The regulator of G-protein signaling 16 (RGS16) is also important for the regulation of cAMP signaling in the SCN (Doi et al, Nat Commun 2011). Circadian coordination of GPCR signaling will be discussed in more detail.


Prof. Masao Doi received his PhD in 2003 from the University of Tokyo, Department of Biophysics and Biochemistry. With the 2 fellowships awarded from the Japan Society for the Promotion of Science he then completed his research at the University of Tokyo and postdoctoral training at The Centre National de la Recherche Scientifique, France. In 2006 he was appointed Assistant Professor of Department of Brain Science at Kobe University Graduate School of Medicine. One year later he was appointed Lecturer of Department of Systems Biology of Graduate School of Pharmaceutical Sciences at Kyoto University. Since 2011 he is Associate Professor of Department of Systems Biology of Graduate School of Pharmaceutical Sciences at Kyoto University.