The direction of transport through the nuclear pore can be inverted

The direction of transport through the nuclear pore can be inverted
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DOI:
10.1073/pnas.96.17.9622
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发表时间:
1999-08-17
影响因子:
11.1
通讯作者:
Weis, K
Weis, K
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Nachury, MV;Weis, K

文献摘要

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大分子跨核膜的转运是一个依赖于包括GT3 Ran在内的可溶性因子的主动过程。Ran-GTP主要位于细胞核中,并且已显示调节货物结合以及输入和输出受体在其各自的靶区室中的释放。最近,它表明,转运的受体货物复合物通过核孔复合物(NPC)不依赖于GTP水解的Ran;霍尔特;以往,易位的机制仍然知之甚少。是,我们表明,通过NPC的运输方向可以被逆转的存在下,高浓度的细胞质Ran-GTP。在这些条件下,两种不同类别的出口货物在没有GTP水解的情况下被运输到细胞核中。反向转运非常迅速,可以被已知的核蛋白输出抑制剂阻断。这些结果表明,NPC的功能作为一个易化的运输通道,允许受体货物复合物的选择性易位,我们的结论是,核质运输的方向主要是由Ran-GTP的区室化分布。
Transport of macromolecules across the nuclear envelope is an active process that depends on soluble factors including the GTPase Ran. Ran-GTP is predominantly located in the nucleus and has been shown to regulate cargo binding and release of import and export receptors in their respective target compartments. Recently, it was shown that transport of receptor-cargo complexes across the nuclear pore complex (NPC) does not depend on GTP-hydrolysis by Ran; holt;ever, the mechanism of translocation is still poorly understood. Were, we show that the direction of transport through the NPC can be inverted in the presence of high concentrations of cytoplasmic Ran-GTP. Under these conditions, two different classes of export cargoes are transported into the nucleus in the absence of GTP hydrolysis. The inverted transport is very rapid and can be blocked by known inhibitors of nuclear protein export. These results suggest that the NPC functions as a facilitated transport channel, allowing the selective translocation of receptor-cargo complexes, We conclude that the directionality of nucleocytoplasmic transport is determined mainly by the compartmentalized distribution of Ran-GTP.