双色MINFLUX揭示了重叠的核进出口路径,这一成果由德州农工大学Siegfried M. Musser课题组经过不懈努力而取得。2025年3月19日出版的《自然》杂志发表了这一最新研究成果。
在这里,该课题组使用3D MINFLUX2来识别核孔支架,然后同时监测核输入和核输出,从而确定两个运输过程都发生在中心孔的重叠区域。而阻止转运的进口复合物在孔隙外围结合,在中心孔区域的转运复合物的轨迹显示出大约40到50纳米直径的环状复合物的偏好,具有最小的周向运动,表明活性依赖于渗透屏障内的限制。孔内的运动速度比溶液中慢约1000倍,并且散布着原基体,表明在一个高度受限的环境中,存在结构约束和/或运输过程中的瞬时结合事件。这些结果表明,高时空精度和减少光漂白是MINFLUX跟踪的主要优势,并且NPC渗透屏障被划分为具有不同功能特性的环形环。
据介绍,核孔复合物(NPC)介导核胞质交换,催化蛋白质和核酸物质在两个方向上的大量流动。进口和出口的不同贩运途径将是避免非生产性冲突和对立运动的优雅解决方案。然而,在毫秒级传输事件的时间尺度上,大分子穿越NPC的三维(3D)纳米尺度时空动力学仍然具有挑战性。
附:英文原文
Title: Overlapping nuclear import and export paths unveiled by two-colour MINFLUX
Author: Sau, Abhishek, Schnorrenberg, Sebastian, Huang, Ziqiang, Bandyopadhyay, Debolina, Sharma, Ankith, Grth, Clara-Marie, Dave, Sandeep, Musser, Siegfried M.
Issue&Volume: 2025-03-19
Abstract: The nuclear pore complex (NPC) mediates nucleocytoplasmic exchange, catalysing a massive flux of protein and nucleic acid material in both directions1. Distinct trafficking pathways for import and export would be an elegant solution to avoid unproductive collisions and opposing movements. However, the three-dimensional (3D) nanoscale spatiotemporal dynamics of macromolecules traversing the NPC remains challenging to visualize on the timescale of millisecond-scale transport events. Here we used 3D MINFLUX2 to identify the nuclear pore scaffold and then to simultaneously monitor both nuclear import and nuclear export, thereby establishing that both transport processes occur in overlapping regions of the central pore. Whereas translocation-arrested import complexes bound at the pore periphery, tracks of translocating complexes within the central pore region revealed a preference for an approximately 40- to 50-nm diameter annulus with minimal circumferential movement, indicating activity-dependent confinement within the permeability barrier. Movement within the pore was approximately 1,000-fold slower than in solution and was interspersed with pauses, indicating a highly restricted environment with structural constraints and/or transient binding events during transport. These results demonstrate that high spatiotemporal precision with reduced photobleaching is a major advantage of MINFLUX tracking, and that the NPC permeability barrier is divided into annular rings with distinct functional properties.
DOI: 10.1038/s41586-025-08738-0
Source: https://www.nature.com/articles/s41586-025-08738-0
Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html