Nuclear localization of the G protein beta 5/R7-regulator of G protein signaling protein complex is dependent on R7 binding protein

J Neurochem. 2010 Jun;113(5):1101-12. doi: 10.1111/j.1471-4159.2010.06616.x. Epub 2010 Jan 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Brain Chemistry / physiology
  • Cell Membrane / metabolism
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Cytoplasm / ultrastructure
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • Fluorescent Antibody Technique
  • GTP-Binding Protein beta Subunits / genetics
  • GTP-Binding Protein beta Subunits / metabolism*
  • Genotype
  • Immunoprecipitation
  • Mice
  • Mice, Knockout
  • Microscopy, Confocal
  • Mutation / physiology
  • Nuclear Localization Signals / physiology*
  • PC12 Cells
  • RGS Proteins / genetics
  • RGS Proteins / metabolism*
  • Rats
  • Transfection


  • DNA, Complementary
  • GTP-Binding Protein beta Subunits
  • Gnb5 protein, mouse
  • Nuclear Localization Signals
  • R7BP protein, mouse
  • RGS Proteins
  • Rgs7 protein, mouse