TY - INPR A1 - Taniguchi, Reiya A1 - Orniacki, Clarisse A1 - Kreysing, Jan Philipp A1 - Zila, Vojtech A1 - Zimmerli, Christian Eugen A1 - Böhm, Stefanie A1 - Turoňová, Beata A1 - Kräusslich, Hans-Georg A1 - Doye, Valérie A1 - Beck, Martin T1 - Nuclear pores safeguard the integrity of the nuclear envelope T2 - bioRxiv N2 - Nuclear pore complexes (NPCs) constitute giant channels within the nuclear envelope that mediate nucleocytoplasmic exchange. NPC diameter is thought to be regulated by nuclear envelope tension, but how such diameter changes are physiologically linked to cell differentiation, where mechanical properties of nuclei are remodeled and nuclear mechanosensing occurs, remains unstudied. Here we used cryo-electron tomography to show that NPCs dilate during differentiation of mouse embryonic stem cells into neural progenitors. In Nup133-deficient cells, which are known to display impaired neural differentiation, NPCs however fail to dilate. By analyzing the architectures of individual NPCs with template matching, we revealed that the Nup133-deficient NPCs are structurally heterogeneous and frequently disintegrate, resulting in the formation of large nuclear envelope openings. We propose that the elasticity of the NPC scaffold mechanically safeguards the nuclear envelope. Our studies provide a molecular explanation for how genetic perturbation of scaffolding components of macromolecular complexes causes tissue-specific phenotypes. Y1 - 2024 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/83055 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-830554 UR - https://www.biorxiv.org/content/10.1101/2024.02.05.578890v1 IS - 2024.02.05.578890 Version 1 PB - bioRxiv ER -