title: New insights into mechanisms of nuclear translocation of G-protein coupled receptors.
abstract: The G-protein coupled receptor (GPCR) signaling was long believed to involve activation of receptor exclusively at the cell surface, followed by its binding to heterotrimeric G-proteins and arrestins to trigger various intracellular signaling cascades, and termination of signaling by internalization of the receptor. It is now accepted that many GPCRs continue to signal after internalization in the endosomes. Since the breakthrough discoveries of nuclear binding sites for their ligands in 1980s, several GPCRs have been detected at cell nuclei. But mechanisms of nuclear localization of GPCRs, many of whom contain putative nuclear localization signals, remain poorly understood to date. Nevertheless, it is known that subcellular trafficking of GPCRs is regulated by members of Ras superfamily of small GTPases, most notably by Rab and Arf GTPases. In this commentary, we highlight several recent studies which suggest novel roles of small GTPases, importins and sorting nexin proteins in the nuclear translocation of GPCRs via vesicular transport pathways. Taken together with increasing evidence forin vivofunctionality of the nuclear GPCRs, better understanding of their trafficking will provide valuable clues in cell biology.
authors.affiliation: a Department of Pharmacology and Therapeutics , McGill University , Montréal , Québec , Canada.|b CHU Sainte-Justine Hospital Research Centre , University of Montréal , Montréal , Québec , Canada.|c Maisonneuve-Rosemont Hospital Research Centre , University of Montréal , Montréal , Québec , Canada.|e Cell Biology Program , Peter Gilgan Centre for Research and Learning , Toronto , Ontario , Canada.
authors.forename: Vikrant K
authors.identifier: 0000-0002-2103-6454
authors.initials: VK
authors.lastname: Bhosle
authors.affiliation: b CHU Sainte-Justine Hospital Research Centre , University of Montréal , Montréal , Québec , Canada.|c Maisonneuve-Rosemont Hospital Research Centre , University of Montréal , Montréal , Québec , Canada.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Rivera
authors.affiliation: a Department of Pharmacology and Therapeutics , McGill University , Montréal , Québec , Canada.|b CHU Sainte-Justine Hospital Research Centre , University of Montréal , Montréal , Québec , Canada.|c Maisonneuve-Rosemont Hospital Research Centre , University of Montréal , Montréal , Québec , Canada.|d Departments of Pediatrics, Ophthalmology and Pharmacology , University of Montréal , Montréal , Québec , Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000378:metabolism*; D019913:Nuclear Localization Signals; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D058305:Sorting Nexins / Q000378:metabolism*
chemical_list: D028884:Karyopherins; D019913:Nuclear Localization Signals; D043562:Receptors, G-Protein-Coupled; D058305:Sorting Nexins
keywords: Rab GTPases; importins; nuclear GPCRs; sorting nexins; vesicular transport