马克斯·普朗克生物物理研究所Bernhard Hampoelz小组近日取得一项新成果。经过不懈努力，他们的最新研究揭示了小GTP酶Ran定义核孔复合体的不对称性。2025年8月18日，国际知名学术期刊《细胞》发表了这一成果。

该课题组研究人员结合低温电子断层扫描、亚断层扫描平均、模板匹配技术，以芽殖酵母和黑腹果蝇为模型，通过活体成像揭示了这一机制。小组通过基因诱导异位核孔，发现核膜外的孔是对称的。该课题组人员进一步证明外周NPC的结构受到小GTP酶Ran的核苷酸状态的影响。他们的研究结果表明，核转运系统是自我调节的，即相同的分子机制控制着运输和运输通道的组成。

据悉，核孔复合物（NPCs）跨越核膜并介导核胞质交换。它们由数百个核孔蛋白组成，说明了大分子组装的结构复杂性。为了确保运输的方向性，不同的核孔蛋白复合物附着在鼻咽癌的细胞质和核表面。这些不对称的结构是如何忠实地组装到对称的支架结构上的，这些支架结构向两边暴露了相同的相互作用表面，这仍然是一个谜。

附：英文原文

Title: The small GTPase Ran defines nuclear pore complex asymmetry

Author: Jenny Sachweh, Mandy Brmel, Sven Klumpe, Anja Becker, Reiya Taniguchi, Marta Anna Kubańska, Verena Pintschovius, Eva Kaindl, Jürgen M. Plitzko, Florian Wilfling, Martin Beck, Bernhard Hampoelz

Issue&Volume: 2025-08-18

Abstract: Nuclear pore complexes (NPCs) bridge across the nuclear envelope and mediate nucleocytoplasmic exchange. They consist of hundreds of nucleoporin building blocks and exemplify the structural complexity of macromolecular assemblies. To ensure transport directionality, different nucleoporin complexes are attached to the cytoplasmic and nuclear face of the NPC. How those asymmetric structures are faithfully assembled onto the symmetric scaffold architecture that exposes the same interaction surfaces to either side remained enigmatic. Here, we combine cryo-electron tomography, subtomogram averaging, and template matching with live imaging to address this question in budding yeast and Drosophila. We genetically induce ectopic nuclear pores and show that pores outside the nuclear envelope are symmetric. We furthermore demonstrate that the peripheral NPC configuration is affected by the nucleotide state of the small GTPase Ran. Our findings indicate that the nuclear transport system is self-regulatory, namely that the same molecular mechanism controls both transport and transport channel composition.

DOI: 10.1016/j.cell.2025.07.025

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00814-1