Dissection of the molecular mechanisms that control the nuclear accumulation of transport factors importin-α and CAS in stressed cells
Dissection of the molecular mechanisms that control the nuclear accumulation of transport factors importin-α and CAS in stressed cells
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DOI：
10.1007/s00018-008-7588-2
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发表时间：
2008-06-01
影响因子：
8
通讯作者：
Stochaj，U.
中科院分区：
文献类型：
--
作者：
Kodiha，M.;Banski，P.;Stochaj，U.
真核细胞的生理状态控制着大量物质的核运输。例如，应激导致经典蛋白质进口的抑制，其特征是几种运输因子的重新分配。因此，输入蛋白α和细胞凋亡易感性蛋白（CAS）在热休克细胞的细胞核中积累；然而，这种重新定位的机制尚不完全清楚。我们现在表明，热量上调了输入α在核包膜上的初始对接，并刺激CAS转运到核内部。此外，热暴露损害了输入α从细胞核的出口，并显著增加其在核质中的保留，而CAS核的出口和保留受到的影响较小。综上所述，我们的研究结果支持热休克在多个水平上调节输入α和CAS核积累的观点。不同应力诱导变化的组合导致热应激细胞中两种转运因子的核浓度。
The physiological state of eukaryotic cells controls nuclear trafficking of numerous cargos. For example, stress results in the inhibition of classical protein import, which is characterized by the redistribution of several transport factors. As such, importin-α and cellular apoptosis susceptibility protein (CAS) accumulate in nuclei of heat-shocked cells; however, the mechanisms underlying this relocation are not fully understood. We now show that heat upregulates the initial docking of importin-α at the nuclear envelope and stimulates the translocation of CAS into the nuclear interior. Moreover, heat exposure compromises the exit of importin-α from nuclei and drastically increases its retention in the nucleoplasm, whereas CAS nuclear exit and retention are less affected. Taken together, our results support the idea that heat shock regulates importin-α and CAS nuclear accumulation at several levels. The combination of different stress-induced changes leads to the nuclear concentration of both transport factors in heat-stressed cells.