Ndrg2 promotes neurite outgrowth of NGF-differentiated PC12 cells

Ndrg2 promotes neurite outgrowth of NGF-differentiated PC12 cells
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DOI:
10.1016/j.neulet.2005.06.055
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发表时间:
2005-11-18
影响因子:
2.5
通讯作者:
Yamada, M
Yamada, M
中科院分区:
医学4区
文献类型:
--
作者:
Takahashi, K;Yamada, M;Yamada, M

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Ndrg2 是 N-myc 下游调节基因的成员。迄今为止,已鉴定出大鼠 Ndrg2 蛋白的两种不同亚型:Ndrg2S 和 Ndrg2L。最近,我们发现大鼠 Ndrg2 是抗抑郁药和 ECT 的新型靶分子。然而,Ndrg2 在中枢神经系统中的功能作用仍不清楚。在本研究中,我们检查了内源性 Ndrg2 的表达、转染的 Ndrg2 蛋白的细胞定位以及 NGF 分化的 PC12 细胞中 Ndrg2 过度表达引起的形态变化。接触NGF后1-2天,神经突开始萌芽;随后的神经突生长持续5天。在此期间,我们通过实时定量PCR评估了Ndrg2 mRNA的表达,发现表达以时间依赖性方式显着增加。有趣的是,V5 缀合的 Ndrg2S 和 Ndrg2L 蛋白在 NGF 分化的 PC 12 中表达,特异性定位于细胞表面膜和生长锥。此外,Ndrg2S 和 Ndrg2L 过度表达促进 NGF 分化的 PC 12 细胞中神经突的伸长。总之,我们的研究结果为 Ndrg2 在中枢神经系统中的生理作用提供了新的见解。 (C) 2005 Elsevier Ireland Ltd. 保留所有权利。
Ndrg2 is a member of the N-myc downstream-regulated genes. Thus far, two different isoforms of rat Ndrg2 protein, Ndrg2S and Ndrg2L, have been identified. Recently, we have identified rat Ndrg2 as a novel target molecule of antidepressants and ECT. The functional role of Ndrg2 in the central nervous system, however, remains unclear. In the present study, we examined the expression of endogenous Ndrg2, cellular localization of transfected Ndrg2 protein, and morphological changes resulting from overexpression of Ndrg2 in NGF-differentiated PC12 cells. Neurites began to sprout 1-2 days after exposure to NGF; subsequent neurite growth continued for 5 days. During this time, we evaluated Ndrg2 mRNA expression by real-time quantitative PCR and found that expression significantly increased in a time-dependent manner. Interestingly, V5-conjugated Ndrg2S and Ndrg2L proteins expressed in NGF-differentiated PC 12 specifically localized to cell surface membranes and growth cones. Moreover, Ndrg2S and Ndrg2L overexpression promoted neurite elongation in NGF-differentiated PC 12 cells. In conclusion, our findings offer novel insights into the physiological roles of Ndrg2 in the central nervous system. (C) 2005 Elsevier Ireland Ltd. All rights reserved.