Grafstein-Dunn E, Young K H, Cockett M I, Khawaja X Z
Wyeth Neuroscience, CN 8000, Princeton, NJ 08543-8000, USA.
Brain Res Mol Brain Res. 2001 Mar 31;88(1-2):113-23. doi: 10.1016/s0169-328x(01)00038-9.
Regulators of G-protein signaling (RGS) proteins are a novel family of GTPase-activating proteins that interact with Galpha subunits of the Gi/o, Gz, Gq and G(12/13) subfamilies to dampen G-protein-coupled receptor (GPCR)-mediated signaling by accelerating intrinsic Galpha-GTPase activity. In the present study, we report on messenger ribonucleic acid (mRNA) localization in rat brain of six RGS genes by in situ hybridization. The distribution patterns of RGS2, RGS13, RGS14 and GAIP (Galpha interacting protein) overlapped in most brain regions examined. Highest regional expression was observed for RGS2 in the cerebral cortical layers, striatum, hippocampal formation, several thalamic and hypothalamic nuclei and hindbrain regions such as the pontine, interpeduncular and dorsal raphe nuclei. Levels of RGS14 mRNA closely paralleled those of RGS2 expression levels throughout most brain regions. RGS13 mRNA was enriched in the hippocampal formation, amygdala, mammillary nuclei as well as the pontine and interpeduncular nuclei. GAIP expression levels were highest in the hippocampal formation with moderate to low levels present in all other regions studied. Of the six RGS genes probed, RGS16 mRNA displayed a discrete localization predominantly in the thalamic midline/intralaminar and principal relay nuclei, and the hypothalamic suprachiasmatic nucleus. RGS1 mRNA signal was not detected in brain. In conclusion, the in situ hybridization studies for RGS2, RGS13, RGS14, RGS16 and GAIP mRNAs extend our knowledge of the distribution of RGS genes expressed in the rat central nervous system, and indicate overlapping RGS-enriched regions that may be indicative of functional diversification in GPCR signaling pathway modulation.
G蛋白信号调节(RGS)蛋白是一类新型的GTP酶激活蛋白,它们与Gi/o、Gz、Gq和G(12/13)亚家族的Gα亚基相互作用,通过加速内在的Gα-GTP酶活性来减弱G蛋白偶联受体(GPCR)介导的信号传导。在本研究中,我们通过原位杂交报告了六个RGS基因在大鼠脑中的信使核糖核酸(mRNA)定位。RGS2、RGS13、RGS14和GAIP(Gα相互作用蛋白)的分布模式在大多数检测的脑区中重叠。在大脑皮层各层、纹状体、海马结构、几个丘脑和下丘脑核以及后脑区域如脑桥、脚间核和中缝背核中观察到RGS2的区域表达最高。在大多数脑区中,RGS14 mRNA的水平与RGS2的表达水平密切平行。RGS13 mRNA在海马结构、杏仁核、乳头体核以及脑桥和脚间核中富集。GAIP的表达水平在海马结构中最高,在所有其他研究区域中为中度至低度。在所检测的六个RGS基因中,RGS16 mRNA主要定位于丘脑中线/板内核和主要中继核以及下丘脑视交叉上核。在脑中未检测到RGS1 mRNA信号。总之,对RGS2、RGS13、RGS14、RGS16和GAIP mRNA的原位杂交研究扩展了我们对大鼠中枢神经系统中表达的RGS基因分布的认识,并表明了RGS富集区域的重叠,这可能表明在GPCR信号通路调节中功能的多样化。