title: GPCR Signaling and Trafficking: The Long and Short of It.
abstract: Emerging findings disclose unexpected components of G protein-coupled receptor (GPCR) signaling and cell biology. Select GPCRs exhibit classical signaling, that is restricted to cell membranes, as well as newly described persistent signaling that depends on internalization of the GPCR bound to β-arrestins. Termination of non-canonical endosomal signaling requires intraluminal acidification and sophisticated protein trafficking machineries. Recent studies reveal the structural determinants of the trafficking chaperones. This review summarizes advances in GPCR signaling and trafficking with a focus on the parathyroid hormone receptor (PTHR) as a prototype, and on the actin-sorting nexin 27 (SNX27)-retromer tubule (ASRT) complex, an endosomal sorting hub responsible for recycling and preservation of cell surface receptors. The findings are integrated into a model of PTHR trafficking with implications for signal transduction, bone growth, and mineral ion metabolism.
authors.affiliation: Cellular Orthopaedic Laboratory, School of Surgery, The University of Western Australia, Nedlands, WA 6009, Australia.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Pavlos
authors.affiliation: Laboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, Department of Structural Biology University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. Electronic address: paf10@pitt.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Friedman
mesh_terms: D000818:Animals; D011992:Endosomes / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D058305:Sorting Nexins / Q000235:genetics / Q000378:metabolism
chemical_list: D044168:Receptor, Parathyroid Hormone, Type 1; D043562:Receptors, G-Protein-Coupled; D058305:Sorting Nexins
keywords: ASRT complex; GPCR; PTHR; SNX27; endosome; retromer