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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Self-regulated viscous channel in the nuclear pore complex
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Self-regulated viscous channel in the nuclear pore complex

机译：核孔复合物中的自调控粘性通道

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摘要

The nuclear pore complex (NPC), the sole gateway for nucleocyto-plasmic exchange in eukaryotic cells, allows for the passive diffusion of small molecules and transport-receptor-facilitated translocation of signal-dependent cargo molecules. Whether small molecules passively diffuse through a single central channel or through multiple holes of a hydrogel network is a subject of debate. Additionally, whether the passive and facilitated transport systems occupy distinct or overlapping physical regions of the NPC remains unclear. Here, we directly test these models using three-dimensional super-resolution fluorescence microscopy of human cells. This approach reveals that a single viscous central channel in the NPC acts as the sole pathway for passive diffusion of various small molecules; transport receptors and their cargo complexes take distinct transport routes in the periphery, which is occluded by phenylalanine-glycine filaments. Furthermore, the passive and facilitated passageways in the NPC are closely correlated, and their conformations can be simultaneously regulated by Importin f)1 (a major transport receptor) and RanGTP (a critical regulator of transport directionality). These results strongly favor a self-regulated viscous channel configuration in native NPCs over the porous hydrogel meshwork model.
机译：核孔复合体（NPC）是真核细胞中核质间交换的唯一通道，它允许小分子的被动扩散和信号依赖性货物分子的转运受体促进的易位。小分子是通过单个中央通道还是通过水凝胶网络的多个孔被动扩散是一个争论的话题。另外，尚不清楚被动运输系统和便利运输系统是否占据NPC的不同或重叠的物理区域。在这里，我们使用人体细胞的三维超分辨率荧光显微镜直接测试这些模型。这种方法揭示了NPC中的单个粘性中心通道是各种小分子被动扩散的唯一途径。转运受体及其货物复合物在外围采取截然不同的转运途径，而苯丙氨酸-甘氨酸丝阻塞了转运途径。此外，NPC中的被动通道和便利通道密切相关，并且它们的构象可以同时由Importin f）1（一种主要的运输受体）和RanGTP（一种重要的运输方向性调节剂）调节。这些结果强烈支持天然NPC的自调节粘性通道构型优于多孔水凝胶网状模型。

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