title: G-protein-coupled receptors signalling at the cell nucleus: an emerging paradigm.
abstract: G-protein-coupled receptors (GPCRs) comprise a wide family of monomeric heptahelical glycoproteins that recognize a broad array of extracellular mediators including cationic amines, lipids, peptides, proteins, and sensory agents. Thus far, much attention has been given towards the comprehension of intracellular signaling mechanisms activated by cell membrane GPCRs, which convert extracellular hormonal stimuli into acute, non-genomic (e.g., hormone secretion, muscle contraction, and cell metabolism) and delayed, genomic biological responses (e.g., cell division, proliferation, and apoptosis). However, with respect to the latter response, there is compelling evidence for a novel intracrine mode of genomic regulation by GPCRs that implies either the endocytosis and nuclear translocation of peripheral-liganded GPCR and (or) the activation of nuclearly located GPCR by endogenously produced, nonsecreted ligands. A noteworthy example of the last scenario is given by heptahelical receptors that are activated by bioactive lipoids (e.g., PGE(2) and PAF), many of which may be formed from bilayer membranes including those of the nucleus. The experimental evidence for the nuclear localization and signalling of GPCRs will be reviewed. We will also discuss possible molecular mechanisms responsible for the atypical compartmentalization of GPCRs at the cell nucleus, along with their role in gene expression.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Fleurimont, Canada. Fernand.Gobeil@USherbrooke.ca
authors.forename: Fernand
authors.initials: F
authors.lastname: Gobeil
authors.forename: Audrey
authors.initials: A
authors.lastname: Fortier
authors.forename: Tang
authors.initials: T
authors.lastname: Zhu
authors.forename: Michela
authors.initials: M
authors.lastname: Bossolasco
authors.forename: Martin
authors.initials: M
authors.lastname: Leduc
authors.forename: Michel
authors.initials: M
authors.lastname: Grandbois
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Heveker
authors.forename: Ghassan
authors.initials: G
authors.lastname: Bkaily
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
authors.forename: David
authors.initials: D
authors.lastname: Barbaz
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D043562:Receptors, G-Protein-Coupled