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| Title | Nuclear pores safeguard the integrity of the nuclear envelope. |
|---|---|
| Journal, issue, pages | Nat Cell Biol, Vol. 27, Issue 5, Page 762-775, Year 2025 |
| Publish date | Apr 9, 2025 |
 Authors | Reiya Taniguchi / Clarisse Orniacki / Jan Philipp Kreysing / Vojtech Zila / Christian E Zimmerli / Stefanie Böhm / Beata Turoňová / Hans-Georg Kräusslich / Valérie Doye / Martin Beck /      |
| PubMed 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 ...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. |
 External links | Nat Cell Biol / PubMed:40205196 / PubMed Central |
| Methods | EM (subtomogram averaging) |
| Resolution | 28.5 - 34.2 Å |
| Structure data |  EMDB-52153: Cytoplasmic ring of the nuclear pore complex from wild-type mouse embryonic stem cell  EMDB-52154: Inner ring of the nuclear pore complex from wild-type mouse embryonic stem cell  EMDB-52155: Nuclear ring of the nuclear pore complex from wild-type mouse embryonic stem cell  EMDB-52156: Cytoplasmic ring of the nuclear pore complex from Nup133-deficient mouse embryonic stem cell  EMDB-52157: Inner ring of the nuclear pore complex from Nup133-deficient mouse embryonic stem cell  EMDB-52158: Nuclear ring of the nuclear pore complex from Nup133-deficient mouse embryonic stem cell  EMDB-52159: Cytoplasmic ring of the nuclear pore complex from wild-type neural progenitors differentiated from mES cells  EMDB-52160: Inner ring of the nuclear pore complex from wild-type neural progenitors differentiated from mES cells  EMDB-52161: Nuclear ring of the nuclear pore complex from wild-type neural progenitors differentiated from mES cells  EMDB-52162: Cytoplasmic ring of the nuclear pore complex from Nup133-deficient neural progenitors differentiated from mES cells  EMDB-52163: Inner ring of the nuclear pore complex from Nup133-deficient neural progenitors differentiated from mES cells  EMDB-52164: Nuclear ring of the nuclear pore complex from Nup133-deficient neural progenitors differentiated from mES cells |
| Source |
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Mus musculus (house mouse)