巴塞尔大学Roderick Y. H. Lim小组在研究中取得进展。他们揭示了核柔蛋白重塑核孔复杂运输屏障的动态组织。2025年12月2日出版的《自然—细胞生物学》杂志发表了这项成果。

在这里，课题组以高速原子力显微镜为主题，辅以体外和体内正交方法，以毫秒分辨率探测NPC中心通道的动态行为。研究组发现核转运因子动态地重塑了连接在NPC通道内的内在无序苯丙氨酸-甘氨酸（FG）结构域，将屏障划分为两个区域：快速波动的环形区域和高度移动的中心塞。在突变的NPC中增加的FG-repeat密度抑制了屏障动力学和受损的运输。值得注意的是，在携带转运因子和正确连接FG结构域的DNA折纸纳米孔中重现了NPC样行为，但在体外FG水凝胶中却没有。因此，NPC的旋转对称结构支持纳米级屏障组织，这与体外FG结构域组件的许多大块特性形成对比。

据了解，核孔复合物（NPCs）介导核仁和细胞质之间大分子的选择性交换，但其运输屏障的组织一直是一个有争议的问题。

附：英文原文

Title: Karyopherins remodel the dynamic organization of the nuclear pore complex transport barrier

Author: Kozai, Toshiya, Fernandez-Martinez, Javier, Kapinos, Larisa E., Gallardo, Paola, van Eeuwen, Trevor, Saladin, Martin, Eliasian, Roi, Mazur, Adam, Zhang, Wenzhu, Tempkin, Jeremy, Panatala, Radhakrishnan, Delgado-Izquierdo, Maria, Escribano-Marin, Raul, Feng, Qingzhou, Lin, Chenxiang, Sali, Andrej, Chait, Brian T., Raveh, Barak, Veenhoff, Liesbeth M., Rout, Michael P., Lim, Roderick Y. H.

Issue&Volume: 2025-12-02

Abstract: Nuclear pore complexes (NPCs) mediate selective exchange of macromolecules between the nucleus and cytoplasm, but the organization of their transport barrier has been a matter of debate. Here we used high-speed atomic force microscopy, complemented with orthogonal in vitro and in vivo approaches, to probe the dynamic behaviour of the NPC central channel at millisecond resolution. We found that nuclear transport factors dynamically remodel intrinsically disordered phenylalanine-glycine (FG) domains tethered within the NPC channel, partitioning the barrier into two zones: a rapidly fluctuating annular region and a highly mobile central plug. Increased FG-repeat density in mutant NPCs dampened barrier dynamics and impaired transport. Notably, NPC-like behaviour was recapitulated in DNA origami nanopores bearing transport factors and correctly tethered FG domains but not in in vitro FG hydrogels. Thus, the rotationally symmetric architecture of NPCs supports a nanoscopic barrier organization that contrasts with many of the bulk properties of in vitro FG-domain assemblies.

DOI: 10.1038/s41556-025-01812-9

Source: https://www.nature.com/articles/s41556-025-01812-9