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Nuclear localization of the G protein beta 5/R7-regulator of G protein signaling protein complex is dependent on R7 binding protein.
- Source :
-
Journal of neurochemistry [J Neurochem] 2010 Jun; Vol. 113 (5), pp. 1101-12. Date of Electronic Publication: 2010 Jan 22. - Publication Year :
- 2010
-
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.
- Subjects :
- 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
Genotype
Immunoprecipitation
Mice
Mice, Knockout
Microscopy, Confocal
Mutation physiology
PC12 Cells
RGS Proteins genetics
Rats
Transfection
GTP-Binding Protein beta Subunits metabolism
Nuclear Localization Signals physiology
RGS Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1471-4159
- Volume :
- 113
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 20100282
- Full Text :
- https://doi.org/10.1111/j.1471-4159.2010.06616.x