Nuclear Pore Transport: Toward an Integrated Perspective

Nuclear pore complexes (NPCs) mediate the selective exchange of proteins and RNAs between nucleus and cytoplasm. Despite decades of study, the molecular mechanism of transport remains debated, particularly the role of FG-nucleoporin dynamics in facilitating translocation. Here, we compare high-resolution single-molecule trajectories obtained with MINFLUX microscopy with earlier correlation-based measurements, revealing that actual pore-crossing events are typically completed within 2-4 localization steps, corresponding to 2-6 ms depending on localization rates. These values closely match transit times obtained from fluorescence fluctuation analysis and align with models in which cargo binding induces transient FG-nucleoporin collapse. Together with recent independent observations, this synthesis supports a converging view of NPC transport as a fast, directional, FG-assisted process. We propose that integrating fluctuation-based and trajectory-based approaches provides a robust framework for reconciling mechanistic hypotheses and refining our understanding of selective gating.