Brain-specific RGS9-2 is localized to the nucleus via its unique proline-rich domain

被引:26
作者
Bouhamdan, M
Michelhaugh, SK
Calin-Jageman, I
Ahern-Djamali, S
Bannon, MJ
机构
[1] Wayne State Univ, Dept Pharmacol, Detroit, MI 48201 USA
[2] Wayne State Univ, Dept Psychiat, Detroit, MI 48201 USA
[3] Wayne State Univ, Dept Behav Neurosci, Detroit, MI 48201 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2004年 / 1691卷 / 2-3期
关键词
RGS9-2; G protein signaling; GTPase activity;
D O I
10.1016/j.bbamcr.2004.01.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 Q,5 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. (C) 2004 Elsevier B.V All rights reserved.
引用
收藏
页码:141 / 150
页数:10
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