Mechanism of the stress-induced collapse of the Ran distribution.
Mechanism of the stress-induced collapse of the Ran distribution.
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DOI：
10.1016/j.yexcr.2005.11.017
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发表时间：
2006-02
影响因子：
3.7
通讯作者：
Yoshinari Yasuda;Y. Miyamoto;T. Saiwaki;Y. Yoneda
中科院分区：
文献类型：
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作者：
Yoshinari Yasuda;Y. Miyamoto;T. Saiwaki;Y. Yoneda
小的GTdR Ran在几个关键的核功能中起着核心作用，包括核质运输，细胞周期进程和核被膜的组装。在先前的研究中，我们发现细胞应激诱导importin α在核内积累，这似乎是由Ran梯度的崩溃引发的，导致经典核转运的下调。我们在这里报告说，减少应激诱导的ATP与细胞质RAN水平的增加。荧光素酶分析表明，细胞应激降低了细胞内ATP水平。用ATP耗竭剂处理细胞改变了Ran的分布。此外，当在氧化应激处理的细胞中引入外源性ATP时，Ran的正常分布得以恢复。此外，与RanGTP结合的importin β1变体的下拉实验表明，氧化应激伴随着细胞内RanGTP水平的降低。这些发现表明，细胞应激诱导的ATP水平的降低导致RanGTP水平的降低和Ran分布的崩溃。
The small GTPase Ran plays a central role in several key nuclear functions, including nucleocytoplasmic transport, cell cycle progression, and assembly of the nuclear envelope. In a previous study, we showed that cellular stress induces the nuclear accumulation of importin α, and that this appears to be triggered by a collapse in the Ran gradient, leading to the down-regulation of classical nuclear transport. We report here that a decrease in stress-induced ATP is associated with an increase in cytoplasmic Ran levels. A luciferin–luciferase assay showed that cellular stress decreased the intracellular levels of ATP. Treatment of the cells with ATP-depleting agents altered the distribution of Ran. Furthermore, when exogenous ATP was introduced in oxidative stress-treated cells, a normal distribution of Ran was restored. In addition, a pull-down experiment with an importin β1 variant that binds to RanGTP showed that oxidative stress was accompanied by a decrease in intracellular RanGTP levels. These findings indicate that the decrease in ATP levels induced by cellular stress causes a decrease in RanGTP levels and a collapse of Ran distribution.