Nuclear localization of G protein beta(5) and regulator of G protein signaling 7 in neurons and brain

The role that G beta (5) regulator of G protein signaling (RGS) complexes p lay in signal transduction in brain remains unknown. The subcellular locali zation of G beta (5) and RGS7 was examined in rat PC12 pheochromocytoma cel ls and mouse brain. Both nuclear and cytosolic localization of G beta (5) a nd RGS7 was evident in PC12 cells by immunocytochemical staining. Subcellul ar fractionation of PC12 cells demonstrated G beta (5) immunoreactivity in the membrane, cytosolic, and nuclear fractions. Analysis by limited proteol ysis confirmed the identity of G beta (5) in the nuclear fraction, Subcellu lar fractionation of mouse brain demonstrated G beta (5) and RGS7 but not G gamma (2/3) immunoreactivity in the nuclear fraction. RGS7 and G beta (5) were tightly complexed in the brain nuclear extract as evidenced by their c oimmunoprecipitation with antiRGS7 antibodies. Chimeric protein constructs containing green fluorescent protein fused to wild-type G beta (5) but not green fluorescent fusion proteins with G beta (1) or a mutant G beta (5) im paired in its ability to bind to RGS7 demonstrated nuclear localization in transfected PC12 cells, These findings suggest that G beta (5) undergoes nu clear translocation in neurons via an RGS-dependent mechanism. The novel in tracellular distribution of G beta (5). RGS protein complexes suggests a po tential role in neurons communicating between classical heterotrimeric G pr otein subunits and/or their effecters at the plasma membrane and the cell n ucleus.