title: Insight into SUCNR1 (GPR91) structure and function.
abstract: SUCNR1 (or GPR91) belongs to the family of G protein-coupled receptors (GPCR), which represents the largest group of membrane proteins in human genome. The majority of marketed drugs targets GPCRs, directly or indirectly. SUCNR1 has been classified as an orphan receptor until a landmark study paired it with succinate, a citric acid cycle intermediate. According to the current paradigm, succinate triggers SUCNR1 signaling pathways to indicate local stress that may affect cellular metabolism. SUCNR1 implication has been well documented in renin-induced hypertension, ischemia/reperfusion injury, inflammation and immune response, platelet aggregation and retinal angiogenesis. In addition, the SUCNR1-induced increase of blood pressure may contribute to diabetic nephropathy or cardiac hypertrophy. The understanding of SUCNR1 activation, signaling pathways and functions remains largely elusive, which calls for deeper investigations. SUCNR1 shows a high potential as an innovative drug target and is probably an important regulator of basic physiology. In order to achieve the full characterization of this receptor, more specific pharmacological tools such as small-molecules modulators will represent an important asset. In this review, we describe the structural features of SUCNR1, its current ligands and putative binding pocket. We give an exhaustive overview of the known and hypothetical signaling partners of the receptor in different in vitro and in vivo systems. The link between SUCNR1 intracellular pathways and its pathophysiological roles are also extensively discussed.
authors.affiliation: Laboratory of Molecular Pharmacology, GIGA-Molecular Biology of Diseases, University of Liège, Liège, Belgium; Laboratory of Medicinal Chemistry, Centre for Interdisciplinary Research on Medicines (CIRM), University of Liège, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Gilissen
authors.affiliation: Laboratory of Experimental Surgery, GIGA-Cardiovascular Sciences, University of Liège, Liège, Belgium; Division of Nephrology, University of Liège Hospital (ULg CHU), Liège, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Jouret
authors.affiliation: Laboratory of Medicinal Chemistry, Centre for Interdisciplinary Research on Medicines (CIRM), University of Liège, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Pirotte
authors.affiliation: Laboratory of Molecular Pharmacology, GIGA-Molecular Biology of Diseases, University of Liège, Liège, Belgium; Laboratory of Medicinal Chemistry, Centre for Interdisciplinary Research on Medicines (CIRM), University of Liège, Belgium. Electronic address: j.hanson@ulg.ac.be.
authors.forename: Julien
authors.initials: J
authors.lastname: Hanson
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled; C557078:SUCNR1 protein, human
keywords: Diabetes; GPR91; Hypertension; Ischemia–reperfusion injury; SUCNR1; Succinate