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bioRxiv · 10.1101/2024.10.08.617205

Annulate Lamellae biogenesis is essential for nuclear pore function

Lin, J.·Agote-Aran, A.·Liao, Y.·Schoch, R.·Ronchi, P.·Cochard, V.·Zhu, R.·Kleiss, C.·Ruff, M.·Chevreux, G.·Schwab, Y.·Klaholz, B.·Sumara, I.
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Abstract

Nuclear pore complexes (NPCs) enable nucleocytoplasmic transport. While NPCs primarily localize to the nuclear envelope (NE), they also appear in cytoplasmic endoplasmic reticulum (ER) membranes called annulate lamellae (AL). Though discovered in the mid-20th century, ALs function and biogenesis remain unclear. Previously considered exclusive to embryonic and malignant cells, we find AL in somatic mammalian cells. Under normal conditions, AL store pre-assembled NPCs (AL-NPCs) that integrate into the NE during G1 to support nuclear expansion. Upon pathological stimuli, AL transfer to the NE is impaired, leading to their cytoplasmic accumulation. RanBP2 (Nup358) is essential for AL biogenesis, with its phenylalanine-glycine (FG) repeats promoting AL-NPC scaffold oligomerization. ER-associated Climp63 (CKAP4) directs AL-NPCs to ER sheets and the NE. This AL-driven nuclear pore formation is complementary to the canonical routes, constituting a distinct NPC assembly pathway. Our work uncovers the biogenesis mechanism of AL and the nuclear function of this key cellular organelle.

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Lin, J., Agote-Aran, A., Liao, Y., Schoch, R., Ronchi, P., Cochard, V., Zhu, R., Kleiss, C., Ruff, M., Chevreux, G., Schwab, Y., Klaholz, B., Sumara, I.. 2024-10-09. Annulate Lamellae biogenesis is essential for nuclear pore function. https://doi.org/10.1101/2024.10.08.617205

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