Nuclear pores safeguard the integrity of the nuclear envelope

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<sup>-/-</sup> 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.

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Publication Details

Journal
Nature Cell Biology
Published
2025-04-09
DOI
https://doi.org/10.1038/s41556-025-01648-3
Citations
21
Primary Topic
Nuclear Structure and Function
Type
article
Field-Weighted Citation Impact
16.93
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Nuclear pores safeguard the integrity of the nuclear envelope

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21 citations
Nature Cell Biology
Nuclear Structure and Function
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Nuclear pores safeguard the integrity of the nuclear envelope

Clarisse Orniacki, Valérie Doye, Beata Turoňová, Reiya Taniguchi, Martin Beck, Hans‐Georg Kräusslich, Vojtěch Žíla, Jan Philipp Kreysing, Stefanie Böhm, Christian E. Zimmerli
article en
21 citations

Abstract

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<sup>-/-</sup> 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.

Nature Cell BiologyVol. 27(5)
Goethe University Frankfurt (DE), Montreal Neurological Institute and Hospital (CA), Centre National de la Recherche Scientifique (FR), Université Paris Cité (FR), Heidelberg University (DE), Institut Jacques Monod (FR), German Center for Infection Research (DE), Max Planck Institute of Biophysics (DE), Heidelberg Engineering (Germany) (DE), RIKEN Center for Integrative Medical Sciences (JP), École Polytechnique Fédérale de Lausanne (CH)
Openalex Percentile: Top 1%
Nuclear Structure and Function
16.93
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