Insight into SUCNR1 (GPR91) structure and function

SUCNRI (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. SUCNRI 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 SUCNRI signaling pathways to indicate local stress that may affect cellular metabolism. SUCNRI 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 SUCNRI activation, signaling pathways and functions remains largely elusive, which calls for deeper investigations. SUCNRI 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 SUCNRI intracellular pathways and its pathophysiological roles are also extensively discussed. (C) 2016 Elsevier Inc. All rights reserved.