G-protein-coupled receptor signaling through Gpr176, Gz, and RGS16 tunes time in the center of the circadian clock [Review].

作者: Kaoru Goto , Masao Doi , Tianyu Wang , Sumihiro Kunisue , Iori Murai

DOI: 10.1507/ENDOCRJ.EJ17-0130

关键词: G protein-coupled receptorBiologyG Protein-Coupled Receptor SignalingReceptorNeuroscienceCircadian rhythmSuprachiasmatic nucleusRegulatorCircadian clockEndocrinologyOrphan receptorInternal medicine

摘要: G-protein-coupled receptors (GPCRs) constitute an immensely important class of drug targets with diverse clinical applications. There are still more than 120 orphan GPCRs whose cognate ligands and physiological functions not known. A set circadian pacemaker neurons that governs daily rhythms in behavior physiology resides the suprachiasmatic nucleus (SCN) brain. Malfunction clock has been linked to a multitude diseases, such as sleeping disorders, obesity, diabetes, cardiovascular cancer, which makes attractive target for development. Here, we review recently identified role Gpr176 SCN. is SCN-enriched GPCR sets pace Even without known ligand, this receptor agonist-independent basal activity reduce cAMP signaling. unique cAMP-repressing G-protein subclass Gz required Gpr176. We also provide overview on regulation signaling, emphasis regulator signaling 16 (RGS16). RGS16 indispensable Developing drugs SCN remains unfulfilled opportunity pharmacology. This argues potential impact focusing purpose tuning body clock.

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