title: The apelin receptor: physiology, pathology, cell signalling, and ligand modulation of a peptide-activated class A GPCR.
abstract: The apelin receptor (AR or APJ) is a class A (rhodopsin-like) G-protein-coupled receptor with wide distribution throughout the human body. Activation of the AR by its cognate peptide ligand, apelin, induces diverse physiological effects including vasoconstriction and dilation, strengthening of heart muscle contractility, angiogenesis, and regulation of energy metabolism and fluid homeostasis. Recently, another endogenous peptidic activator of the AR, Toddler/ELABELA, was identified as having a crucial role in zebrafish (Danio rerio) embryonic development. The AR is also implicated in pathologies including cardiovascular disease, diabetes, obesity, and cancer, making it a promising therapeutic target. Despite its established importance, the precise roles of AR signalling remain poorly understood. Moreover, little is known about the mechanisms of peptide-AR activation. Additional complexity arises from modulation of the AR by 2 endogenous peptide ligands, both with multiple bioactive isoforms of variable length and distribution. The various apelin and Toddler/ELABELA isoforms may also produce distinct cellular effects. Further complexity arises through formation of functionally distinct heterodimers between the AR and other G-protein-coupled receptors. This minireview outlines key (patho)physiological actions of the AR, addresses what is known about signal transduction downstream of AR activation, and concludes by discussing unique properties of the endogenous peptidic ligands of the AR.
authors.affiliation: a Department of Biochemistry & Molecular Biology, Dalhousie University, Halifax, NS B3H 4R2, Canada.
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Chapman
authors.forename: Denis J
authors.initials: DJ
authors.lastname: Dupré
authors.forename: Jan K
authors.initials: JK
authors.lastname: Rainey
mesh_terms: D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004625:Embryo, Nonmammalian / Q000196:embryology; D047108:Embryonic Development / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D029961:Zebrafish Proteins; C586716:toddler peptide, zebrafish
keywords: APJ; APLNR; RCPG activé par un peptide; apelinergic system; peptide-activated GPCR; signal transduction; système apelinergique; transduction de signal