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Published on: November 17, 2009
Brain-specific RGS9-2 is localized to the nucleus via its unique proline-rich domain
Mohamad Bouhamdan1, Sharon Kay Michelhaugh, Irina Calin-Jageman
1Department of Psychiatry, Wayne State University School of Medicine, 540 E. Canfield, 2309 Scott Hall, Detroit, MI 48201, USA.
Abstract:
Brain-specific regulator of G protein signaling 9 (RGS9-2) is a member of a family of proteins that can function as GTPase-activating proteins for heterotrimeric G proteins. In the present study, we examined the intracellular distribution of RGS9-2 in native brain tissue and transfected cells. Immunocytochemical and immunoblot experiments revealed an unexpectedly high proportion of RGS9-2 within the nuclei of forebrain neurons. A similar intracellular distribution was seen in transfected COS-7 cells. The RGS9 binding partner G(beta5) further enhanced the nuclear localization of RGS9-2, but did not affect the strongly cytoplasmic localization of RGS9-1, the retinal form of RGS9. Deletion construct analysis revealed that the unique polyproline-rich C-terminus of brain-specific RGS9-2 contains sequences necessary and sufficient to target RGS9 to the nucleus of COS-7 cells, as well as cultured striatal neurons. Furthermore, RGS9-2 transfection increased the transcriptional activity of a neuronal gene construct normally expressed in RGS9-positive neurons, suggesting that nuclear RGS9 directly or indirectly regulates transcription in vivo. The nuclear localization of RGS9-2 suggests a heretofore-unanticipated role for this brain-specific protein in transducing signals to the nuclei of forebrain neurons.
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