López-Aranda Manuel F, Acevedo Maria J, Carballo Francisco J, Gutiérrez Antonia, Khan Zafar U
Departamento de Medicina y Centro de Investigaciones Medico Sanitarias, Facultad de Medicina, Universidad de Málaga, Campus Teatinos, 29071-Málaga, Spain.
Eur J Neurosci. 2006 Jun;23(11):2971-82. doi: 10.1111/j.1460-9568.2006.04838.x.
Regulator of G-protein signalling (RGS)12 and -14 proteins possess the RGS domain, Ras-binding domains and the GoLoco motif. Emerging evidence suggests that these proteins are involved in several cellular functions in addition to stimulation of GTPase activity of G-protein alpha subunits. However, our understanding of the role of the two proteins in brain function remains marginal. Here, we have studied the expression pattern of RGS12 and RGS14 proteins in brain at regional, cellular and subcellular levels. Both proteins were expressed throughout the brain regions, including cortex, hippocampus, striatum, thalamus and substantia nigra. The most intense immunostaining for RGS12 was seen in cortex and that of RGS14 was found in striatum. In cortex, RGS12 and RGS14 proteins were associated with pyramidal and nonpyramidal cell types. Apical dendrites of pyramidal cells were also labelled. RGS12 was found in both nuclear and cytoplasmic compartments. In contrast to RGS12 protein, RGS14 was localized in astrocytes in addition to neurons. Pyramidal cells in the CA1 area showed labelling for both RGS proteins. The presence of RGS12 was predominantly nuclear in the striatum of rat brain; however, the labelling of this protein was non-nuclear in adult monkey brain. To our surprise, in 1-month-old monkey brain the immunostaining pattern of the same protein was changed to nuclear. Non-nuclear staining for RGS12 was also evident in thalamus of adult monkey brain; however, in 1-month-old monkey brain, it was seen into two different populations, one with nuclear and the other with cytoplasmic staining. Both RGS12 and RGS14 were exclusively localized at postsynaptic sites of excitatory synapses. Our results demonstrate a highly dynamic expression pattern of RGS12 and RGS14 proteins in the central nervous system, and support the view that these proteins may participate not only in G-protein receptor signalling pathways but also in other cellular activities.
G蛋白信号调节因子(RGS)12和-14蛋白具有RGS结构域、Ras结合结构域和GoLoco基序。新出现的证据表明,这些蛋白除了能刺激G蛋白α亚基的GTP酶活性外,还参与多种细胞功能。然而,我们对这两种蛋白在脑功能中的作用的了解仍然有限。在这里,我们研究了RGS12和RGS14蛋白在脑的区域、细胞和亚细胞水平上的表达模式。这两种蛋白在整个脑区均有表达,包括皮质、海马、纹状体、丘脑和黑质。RGS12的免疫染色在皮质最为强烈,而RGS14的免疫染色则在纹状体中最为明显。在皮质中,RGS12和RGS14蛋白与锥体细胞和非锥体细胞类型相关。锥体细胞的顶端树突也有标记。RGS12存在于细胞核和细胞质中。与RGS12蛋白不同,RGS14除了在神经元中表达外,还定位于星形胶质细胞中。CA1区的锥体细胞对这两种RGS蛋白均有标记。RGS12在大鼠脑纹状体中主要定位于细胞核;然而,在成年猴脑中,该蛋白的标记是非核性的。令我们惊讶的是,在1个月大的猴脑中,同一蛋白的免疫染色模式变为核性。RGS12在成年猴脑丘脑中的非核染色也很明显;然而,在1个月大的猴脑中,它出现在两个不同的群体中,一个群体为核染色,另一个群体为细胞质染色。RGS12和RGS14均仅定位于兴奋性突触的突触后位点。我们的结果表明,RGS12和RGS14蛋白在中枢神经系统中具有高度动态的表达模式,并支持这样一种观点,即这些蛋白不仅可能参与G蛋白受体信号通路,还可能参与其他细胞活动。