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Nuclear pores safeguard the integrity of the nuclear envelope
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Journal Article
Nuclear pores safeguard the integrity of the nuclear envelope
2025
Overview
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.
Taniguchi et al. structurally analyse nuclear pore complex architecture in situ during differentiation, which is associated with mechanical constraints on the nuclear envelope. They link nuclear pore complex elasticity to nuclear envelope integrity in differentiation.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/100
/ 14/19
/ Animals
/ Biomedical and Life Sciences
/ Embryology and Organogenesis
/ Embryonic Stem Cells - metabolism
/ Mice
/ Mouse Embryonic Stem Cells - metabolism
/ Mouse Embryonic Stem Cells - ultrastructure
/ Nuclear Envelope - metabolism
/ Nuclear Envelope - ultrastructure
/ Nuclear Pore - ultrastructure
/ Nuclear Pore Complex Proteins - deficiency
/ Nuclear Pore Complex Proteins - genetics
