title: The G protein-coupled receptor N-terminus and receptor signalling: N-tering a new era.
abstract: G protein-coupled receptors (GPCRs) are a vast family of membrane-traversing proteins, essential to the ability of eukaryotic life to detect, and mount an intracellular response to, a diverse range of extracellular stimuli. GPCRs have evolved with archetypal features including an extracellular N-terminus and intracellular C-terminus that flank a transmembrane structure of seven sequential helices joined by intracellular and extracellular loops. These structural domains contribute to the ability of a GPCR to be correctly synthesised and inserted into the cell membrane, to interact with its cognate ligand(s) and to couple with signal-transducing heterotrimeric G proteins, allowing the activated receptor to selectively modulate a number of signalling cascades. Whilst well known for its importance in receptor translation and trafficking, the GPCR N-terminus is underexplored as a participant in receptor signalling. This review aims to discuss and integrate recent advances in knowledge of the vital roles of the GPCR N-terminus in receptor signalling.
authors.affiliation: Molecular Pharmacology Group, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW 2010, Australia. Electronic address: j.coleman@victorchang.edu.au.
authors.forename: James L J
authors.initials: JL
authors.lastname: Coleman
authors.affiliation: Molecular Pharmacology Group, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW 2010, Australia.
authors.forename: Tony
authors.initials: T
authors.lastname: Ngo
authors.affiliation: Molecular Pharmacology Group, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW 2010, Australia. Electronic address: n.smith@victorchang.edu.au.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Smith
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D006801:Humans; D008958:Models, Molecular; D010447:Peptide Hydrolases / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D043562:Receptors, G-Protein-Coupled; D010447:Peptide Hydrolases
keywords: G protein-coupled receptor; GPCR; N-terminus; Proteolysis; Signalling