Karyopherins remodel the dynamic organization of the nuclear pore complex transport barrier
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.
Authors
- Artur Mazur (ORCID: https://orcid.org/0000-0001-5393-3515)
- Barak Raveh (ORCID: https://orcid.org/0000-0002-2073-3936)
- Wenzhu Zhang (ORCID: https://orcid.org/0009-0001-3154-871X)
- Roderick Y. H. Lim (ORCID: https://orcid.org/0000-0001-5015-6087)
- Toshiya Kozai (ORCID: https://orcid.org/0009-0007-5273-3926)
- Andrej Săli (ORCID: https://orcid.org/0000-0003-0435-6197)
- Chenxiang Lin (ORCID: https://orcid.org/0000-0001-7041-1946)
- Qingzhou Feng
- Javier Fernández-Martı́nez (ORCID: https://orcid.org/0000-0003-0567-498X)
- Liesbeth M. Veenhoff (ORCID: https://orcid.org/0000-0002-0158-4728)
- Maria Delgado-Izquierdo (ORCID: https://orcid.org/0009-0002-8821-5809)
- Paola Gallardo (ORCID: https://orcid.org/0000-0002-8801-0355)
- Michael P. Rout (ORCID: https://orcid.org/0000-0003-2010-706X)
- Radhakrishnan Panatala
- Trevor van Eeuwen (ORCID: https://orcid.org/0000-0003-0549-1702)
- Brian T. Chait (ORCID: https://orcid.org/0000-0003-3524-557X)
- Jeremy O. B. Tempkin (ORCID: https://orcid.org/0000-0002-1602-6649)
- Larisa E. Kapinos (ORCID: https://orcid.org/0000-0001-6101-0876)
- Roi Eliasian
- Martin Saladin
- Raul Escribano-Marin
Institutions
- Ikerbasque (ES)
- Lawrence Livermore National Laboratory (US)
- University Medical Center Groningen (NL)
- Consejo Superior de Investigaciones Científicas (ES)
- University of Groningen (NL)
- University of California, San Francisco (US)
- University of Basel (CH)
- Hebrew University of Jerusalem (IL)
- Yale University (US)
- Quantitative BioSciences (US)
- Centro Andaluz de Biología del Desarrollo (ES)
- Fundación Biofísica Bizkaia (ES)
- Rockefeller University (US)
- Junta de Andalucía (ES)
- Universidad Pablo de Olavide (ES)
Publication Details
- Journal
- Nature Cell Biology
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1038/s41556-025-01812-9
- Citations
- 2
- Primary Topic
- Nuclear Structure and Function
- Type
- article
- Field-Weighted Citation Impact
- 1.61