Nuclear pores safeguard the integrity of the nuclear envelope

被引：0

作者：

Reiya Taniguchi ^{[1
]}

Clarisse Orniacki ^{[7
]}

Jan Philipp Kreysing ^{[2
]}

Vojtech Zila ^{[8
]}

Christian E. Zimmerli ^{[1
]}

Stefanie Böhm ^{[3
]}

Beata Turoňová ^{[4
]}

Hans-Georg Kräusslich ^{[9
]}

Valérie Doye ^{[1
]}

Martin Beck ^{[10
]}

机构：

[1] Department of Molecular Sociology, Max Planck Institute of Biophysics, Frankfurt am Main

[2] Université Paris Cité, CNRS, Institut Jacques Monod, Paris

[3] IMPRS on Cellular Biophysics, Frankfurt am Main

[4] Department of Infectious Diseases, Virology, Heidelberg University, Heidelberg

[5] German Centre for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg

[6] Institute of Biochemistry, Goethe University Frankfurt, Frankfurt am Main

[7] RIKEN Center for Integrative Medical Sciences, Yokohama, Tsurumi-ku

[8] The Neuro – Montreal Neurological Institute and Hospital, McGill University, Montreal, QC

[9] AskBio GmbH, Heidelberg

[10] Institute of Physics, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne

来源：

Nature Cell Biology | 2025年 / 27卷 / 5期

基金：

欧洲研究理事会;

关键词：

D O I：

10.1038/s41556-025-01648-3

中图分类号：

学科分类号：

摘要：

Nuclear pore complexes (NPCs) mediate nucleocytoplasmic exchange, which is essential for eukaryotes. Mutations in the central scaffolding components of NPCs are associated with genetic diseases, but how they manifest only in specific tissues remains unclear. This is exemplified in Nup133-deficient mouse embryonic stem cells, which grow normally during pluripotency, but differentiate poorly into neurons. Here, using an innovative in situ structural biology approach, we show that Nup133−/− mouse embryonic stem cells have heterogeneous NPCs with non-canonical symmetries and missing subunits. During neuronal differentiation, Nup133-deficient NPCs frequently disintegrate, resulting in abnormally large nuclear envelope openings. We propose that the elasticity of the NPC scaffold has a protective function for the nuclear envelope and that its perturbation becomes critical under conditions that impose an increased mechanical load onto nuclei. © The Author(s) 2025.

引用

页码：762 / 775

页数：13

共 85 条

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