Brain-specific RGS9-2 is localized to the nucleus via its unique proline-rich domain
Brain-specific RGS9-2 is localized to the nucleus via its unique proline-rich domain
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DOI：
10.1016/j.bbamcr.2004.01.005
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发表时间：
2004-05-03
影响因子：
5.1
通讯作者：
Bannon, MJ
中科院分区：
文献类型：
--
作者：
Bouhamdan, M;Michelhaugh, SK;Bannon, MJ
脑特异性G蛋白信号转导调节因子9（RGS 9 -2）是一个蛋白质家族的成员，其可以作为异源三聚体G蛋白的GTP酶激活蛋白发挥作用。在本研究中，我们研究了RGS 9 -2在天然脑组织和转染细胞中的细胞内分布。免疫细胞化学和免疫印迹实验揭示了一个出乎意料的高比例的RGS 9 -2内的前脑神经元的核。在转染的COS-7细胞中观察到类似的细胞内分布。RGS 9结合配偶体Q15进一步增强RGS 9 -2的核定位，但不影响RGS 9 -1（RGS 9的视网膜形式）的强烈细胞质定位。缺失构建体分析显示，脑特异性RGS 9 -2的独特的富含聚脯氨酸的C-末端含有将RGS 9靶向COS-7细胞以及培养的纹状体神经元的细胞核所必需和足够的序列。此外，RGS 9 -2转染增加了通常在RGS 9阳性神经元中表达的神经元基因构建体的转录活性，表明核RGS 9直接或间接调节体内转录。RGS 9 -2的核定位表明这种脑特异性蛋白在将信号转导到前脑神经元的核中具有迄今为止未预料到的作用。(C)2004 Elsevier B.V保留所有权利。
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.