Differential expression patterns of NDRG family proteins in the central nervous system
Differential expression patterns of NDRG family proteins in the central nervous system
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DOI：
10.1369/jhc.7a7323.2007
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发表时间：
2008-02-01
影响因子：
3.2
通讯作者：
Miyata, Toshiyuki
中科院分区：
文献类型：
--
作者：
Okuda, Tomohiko;Kokame, Koichi;Miyata, Toshiyuki
哺乳动物N-myc下游调节基因(NDRG)家族由四种蛋白组成：NDRG1、NDRG2、NDRG3和NDRG4。NDRG1是一种与应激反应、细胞生长和分化相关的细胞内蛋白，已被深入研究。NDRG1基因的无义突变导致遗传性运动和感觉神经病，4D型Charcot-Marie-Tooth病。我们之前建立了Ndrg1缺陷小鼠，发现它们表现出由严重脱髓鞘引起的周围神经变性，但复杂的运动能力仍保持不变。这些结果表明，其他NDRG家族蛋白可能弥补了中枢神经系统中NDRG1的缺陷。在这项研究中，我们提出了针对NDRG蛋白家族每个成员的特异性抗体，并检测了它们在小鼠大脑中的细胞表达模式。在大脑中，NDRG1和NDRG2分别定位于少突胶质细胞和星形胶质细胞，而NDRG3和NDRG4则普遍存在。在小脑中，NDRG1和NDRG4定位于Purkinje细胞，NDRG2定位于Bergmann胶质细胞。NDRG3在大多数细胞的胞核中表达。这些表达模式证明了NDRG家族蛋白的细胞类型特异性和普遍存在的定位。每个NDRG可能在大脑中的特定细胞中扮演部分冗余的角色。
The N-myc downstream-regulated gene (NDRG) family consists of four proteins: NDRG1, NDRG2, NDRG3, and NDRG4 in mammals. NDRG1 has been thoroughly studied as an intracellular protein associated with stress response, cell growth, and differentiation. A nonsense mutation in the NDRG1 gene causes hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease type 4D. We previously generated Ndrg1-deficient mice and found that they exhibited peripheral nerve degeneration caused by severe demyelination, but that the complicated motor abilities were retained. These results implied that other NDRG family proteins may compensate for the NDRG1 deficiency in the central nervous system. In this study we raised specific antibodies against each member of the NDRG protein family and examined their cellular expression patterns in the mouse brain. In the cerebrum, NDRG1 and NDRG2 were localized in oligodendrocytes and astrocytes, respectively, whereas NDRG3 and NDRG4 were ubiquitous. In the cerebellum, NDRG1 and NDRG4 were localized in Purkinje cells and NDRG2 in Bergmann glial cells. NDRG3 was detected in the nuclei in most cells. These expression patterns demonstrated the cell type-specific and ubiquitous localization of the NDRG family proteins. Each NDRG may play a partially redundant role in specific cells in the brain.