Heat-shock induced nuclear retention and recycling inhibition of importin α
Heat-shock induced nuclear retention and recycling inhibition of importin α
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DOI：
10.1111/j.1356-9597.2004.00734.x
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发表时间：
2004-05-01
期刊：
影响因子：
2.1
通讯作者：
Imamoto, N
中科院分区：
文献类型：
--
作者：
Furuta, M;Kose, S;Imamoto, N
热休克诱导强烈的应激反应并改变细胞生理的方方面面，这涉及到各种蛋白质核质分布的动态变化。真核细胞中存在许多不同的核质转运途径，但如何在不同的细胞条件下调节一条特定的转运途径仍然难以捉摸。本研究的结果表明，在热休克细胞中，由输入素α/β介导的常规核输入下调，而70kD热休克同源蛋白的核输入上调。在参与调节常规核进口的因素中，在热休克反应中，核内大量积累了Importinα。对Importinα在光漂白后的荧光恢复和在光漂白研究中的荧光损失的行为的分析表明，在热休克细胞中，核Importinα的流动性变得较低，其核质循环受到损害。这些数据与生化和细胞学研究很好地吻合。我们目前的数据表明，热休克诱导了Importinα的核积聚、核滞留和再循环抑制，从而抑制了常规的核进口。这表明了一种新的调节机制，使细胞适应环境变化，如热休克。
Heat-shock induces a strong stress response and modifies all aspects of cellular physiology, which involves dynamic changes in the nucleocytoplasmic distributions of a variety of proteins. Many distinct nucleocytoplasmic transport pathways exist in eukaryotic cells, but how a particular transport pathway is regulated under different cellular conditions remains elusive. The finding of this study indicate that conventional nuclear import, which is mediated by importin alpha/beta, is down-regulated, while the nuclear import of 70 kD heat-shock cognate protein is up-regulated in heat-shock cells. Among the factors involved in the mediation of the conventional nuclear import, significant levels of importin alpha accumulate in the nucleus in response to heat-shock. An analysis of the behaviour of importin alpha with fluorescence recovery after photobleaching and fluorescence loss in photobleaching studies show that nuclear importin alpha becomes less mobile and its nucleocytoplasmic recycling is impaired in heat-shock cells. These data coincided well with biochemical and cytological studies. Our present data show that heat-shock induces the nuclear accumulation, nuclear retention, and recycling inhibition of importin alpha, resulting in the suppression of conventional nuclear import. This suggests a new regulatory mechanism for the adaptation of cells to environmental changes, such as heat-shock.