title: Nuclear localization of the G protein beta 5/R7-regulator of G protein signaling protein complex is dependent on R7 binding protein.
abstract: The neuronally expressed G beta(5) subunit is the most structurally divergent among heterotrimeric G beta isoforms and unique in its ability to heterodimerize with the R7 subfamily of regulator of G protein signaling (RGS) proteins. The complex between G beta(5) and R7-type RGS proteins targets the cell nucleus by an unknown mechanism. Although the nuclear targeting of the G beta(5)/R7-RGS complex is proposed to involve the binding of R7-binding protein (R7BP), this theory is challenged by the observations that endogenous R7BP is palmitoylated, co-localizes strongly with the plasma membrane, and has never been identified in the cytosol or nucleus of native neurons or untreated cultured cells. We show here mutant RGS7 lacking the N-terminal Disheveled, EGL-10, Pleckstrin homology domain is expressed in transfected cells but, unlike wild-type RGS7, is excluded from the cell nucleus. As the Disheveled, EGL-10, Pleckstrin homology domain is essential for R7BP binding to RGS7, we studied the subcellular localization of G beta(5) in primary neurons and brain from mice deficient in R7BP. The level of endogenous nuclear G beta(5) and RGS7 in neurons and brains from R7BP knockout mice is reduced by 50-70%. These results suggest that R7BP contributes significantly to the nuclear localization of endogenous G beta(5)/R7-RGS complex in brain.
authors.affiliation: Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1752, USA.
authors.forename: Leelamma M
authors.initials: LM
authors.lastname: Panicker
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhang
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Posokhova
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gastinger
authors.forename: Kirill A
authors.initials: KA
authors.lastname: Martemyanov
authors.forename: William F
authors.initials: WF
authors.lastname: Simonds
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005455:Fluorescent Antibody Technique; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009154:Mutation / Q000502:physiology; D019913:Nuclear Localization Signals / Q000502:physiology*; D016716:PC12 Cells; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D044387:GTP-Binding Protein beta Subunits; C094668:Gnb5 protein, mouse; D019913:Nuclear Localization Signals; C499440:R7BP protein, mouse; D020710:RGS Proteins; C492038:Rgs7 protein, mouse