title: R7BP augments the function of RGS7*Gbeta5 complexes by a plasma membrane-targeting mechanism.
abstract: The RGS7 (R7) family of G protein regulators, Gbeta5, and R7BP form heterotrimeric complexes that potently regulate the kinetics of G protein-coupled receptor signaling. Reversible palmitoylation of R7BP regulates plasma membrane/nuclear shuttling of R7*Gbeta5*R7BP heterotrimers. Here we have investigated mechanisms whereby R7BP controls the function of the R7 family. We show that unpalmitoylated R7BP undergoes nuclear/cytoplasmic shuttling and that a C-terminal polybasic motif proximal to the palmitoylation acceptor sites of R7BP mediates nuclear localization, palmitoylation, and plasma membrane targeting. These results suggest a novel mechanism whereby palmitoyltransferases and nuclear import receptors both utilize the C-terminal domain of R7BP to determine the trafficking fate of R7*Gbeta5*R7BP heterotrimers. Analogous mechanisms may regulate other signaling proteins whose distribution between the plasma membrane and nucleus is controlled by palmitoylation. Lastly, we show that cytoplasmic RGS7*Gbeta5*R7BP heterotrimers and RGS7*Gbeta5 heterodimers are equivalently inefficient regulators of G protein-coupled receptor signaling relative to plasma membrane-bound heterotrimers bearing palmitoylated R7BP. Therefore, R7BP augments the function of the complex by a palmitoylation-regulated plasma membrane-targeting mechanism.
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Drenan
authors.forename: Craig A
authors.initials: CA
authors.lastname: Doupnik
authors.forename: Muralidharan
authors.initials: M
authors.lastname: Jayaraman
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Buchwalter
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Kaltenbronn
authors.forename: James E
authors.initials: JE
authors.lastname: Huettner
authors.forename: Maurine E
authors.initials: ME
authors.lastname: Linder
authors.forename: Kendall J
authors.initials: KJ
authors.lastname: Blumer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000502:physiology; D044387:GTP-Binding Protein beta Subunits / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology*; D019913:Nuclear Localization Signals; D019308:Palmitic Acid / Q000378:metabolism; D049294:Phospholipid Transfer Proteins / Q000502:physiology; D021381:Protein Transport; D020710:RGS Proteins / Q000737:chemistry / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction; D014982:Xenopus laevis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C490611:GNB5 protein, human; D044387:GTP-Binding Protein beta Subunits; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019913:Nuclear Localization Signals; C493422:PLSCR1 protein, human; D049294:Phospholipid Transfer Proteins; C499440:R7BP protein, mouse; D020710:RGS Proteins; C492039:RGS7 protein, human; C464657:RGS9BP protein, human; D043562:Receptors, G-Protein-Coupled; D019308:Palmitic Acid