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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.
Biochimica Et Biophysica Acta
|April 28, 2004
Summary
Brain-specific regulator of G protein signaling 9 (RGS9-2) is found in neuron nuclei, suggesting a new role in regulating gene transcription. This finding highlights RGS9-2
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Regulators of G protein signaling (RGS) proteins modulate G protein signaling pathways.
- RGS9-2 is a brain-specific RGS protein.
- The intracellular localization of RGS9-2 is not well understood.
Purpose of the Study:
- To investigate the intracellular distribution of RGS9-2 in the brain.
- To determine the functional implications of RGS9-2's localization.
Main Methods:
- Immunocytochemistry and immunoblotting in native brain tissue and transfected cells.
- Analysis of RGS9-2 localization with its binding partner G(beta5).
- Deletion construct analysis to identify nuclear localization signals.
- Assessment of transcriptional activity in transfected neuronal gene constructs.
Main Results:
- A significant proportion of RGS9-2 was found in the nuclei of forebrain neurons.
- G(beta5) enhanced the nuclear localization of RGS9-2, unlike RGS9-1.
- The C-terminus of RGS9-2 contains sequences essential for nuclear targeting.
- RGS9-2 transfection increased the transcriptional activity of a neuronal gene.
Conclusions:
- RGS9-2 is predominantly localized to the nuclei of forebrain neurons.
- Nuclear RGS9-2 may directly or indirectly regulate gene transcription in vivo.
- This suggests a novel role for RGS9-2 in signal transduction within the brain.
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