Differential expression of members of the RCAN family of calcineurin regulators suggests selective functions for these proteins in the brain
Differential expression of members of the RCAN family of calcineurin regulators suggests selective functions for these proteins in the brain
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DOI：
10.1111/j.1460-9568.2007.05749.x
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发表时间：
2007-09-01
影响因子：
3.4
通讯作者：
Arbones, Maria L.
中科院分区：
文献类型：
--
作者：
Porta, Silvia;Marti, Eulalia;Arbones, Maria L.
RCAN又称唐氏综合症关键区-1(DSCR1)样蛋白，又称调节性钙调神经磷酸酶相互作用蛋白(MCIP)或钙压素，是钙调神经磷酸酶的调节者，钙调神经磷酸酶是一种钙依赖的蛋白磷酸酶，参与多种神经元功能。尽管rcan蛋白在脑生理学中具有潜在的重要性，但人们对其在中枢神经系统中的相对丰度和分布模式知之甚少。在这项研究中，我们报告了rcan mRNA转录本和蛋白在小鼠脑中的表达和分布。RT-PCR法和Western印迹分析表明，RCAN1-1、RCAN1-2、Rcan2-1、Rcan2-3和Rcan3及其相应的蛋白产物(RCAN1-L、RCAN1-S、RCAN2-L、RCAN2S和RCAN3)均存在于所研究的每个成年小鼠脑区。在出生后的早期阶段，所有的蛋白质异构体也在这些相同的大脑区域表达。在区域内，RCAN1·L、RCAN1·S、RCAN2·L和RCAN3四个基因在不同区域和发育阶段存在差异表达，而RCAN2·S在不同地区和不同发育阶段表达差异较大。详细的免疫组织化学分析显示，rcan蛋白在细胞和亚细胞中的分布存在显著差异。在成人中，RCAN1主要表达在整个大脑的神经纤维束中。虽然RCAN3的水平较低，但在整个神经束中也能检测到RCAN3。相反，RCAN2在散在神经元中高表达，在胞核和胞浆中均有表达。有趣的是，RCAN2是在胶质细胞中检测到的rcan家族中唯一的成员。最后，RCAN在出生后早期的表达模式与成人不同，在不同的脑区，其分布和相对丰度都不同，这表明这些蛋白的表达可能在神经元分化过程中受到调节。这里显示的rcan蛋白的非重叠表达模式突出了不同生理情景的存在，因此暗示了大脑中不同的rcan功能活动，这取决于细胞背景和发育阶段。
RCANs, also called Down Syndrome Critical Region-1 (DSCR1)-like proteins, Modulatory Calcineurin Interacting Proteins (MCIPs) or calcipressins, are regulators of calcineurin, a Ca2+-dependent protein phosphatase involved in several neuronal functions. Despite the potential importance of the RCAN proteins in brain physiology, very little is known about their relative abundance and distribution patterns in the central nervous system. In this study we report the expression and distribution of RCAN mRNA transcripts and proteins in the mouse brain. RT-PCR and Western blot analysis showed that all Rcan mRNAs (Rcan1-1, Rcan1-2, Rcan2-1, Rcan2-3 and Rcan3) and their corresponding protein products (RCAN1-L, RCAN1-S, RCAN2-L, RCAN2-S and RCAN3) are present in every adult mouse brain region examined. All protein isoforms are also expressed in these same brain regions at early postnatal stages. Within regions, RCAN1-L, RCAN1-S, RCAN2-L and RCAN3 are differentially expressed depending on the region and developmental stage, whereas RCAN2-S is distributed homogeneously. Detailed immunohistochemical analysis revealed significant differences in the cellular and subcellular distributions of RCAN proteins. In the adult, RCAN1 was mainly expressed in the neuropil throughout the brain. Although at lower levels, RCAN3 was also detected throughout the neuropil. In contrast, RCAN2 was highly expressed in scattered neurons, in both the nucleus and the cytoplasm. Interestingly, RCAN2 is the only member of the RCAN family that was detected in glial cells. Finally, the expression patterns of RCANs at early postnatal stages differed from those of the adult, in different brain areas, in both their distributions and relative abundance, suggesting that the expression of these proteins could be regulated during neuronal differentiation. The nonoverlapping expression patterns of the RCAN proteins shown here highlight the existence of different physiological scenarios and therefore suggest different RCAN functional activities in the brain, depending on the cellular context and developmental stage.