How macromolecular complexes are assembled in the correct cellular locations is an important question in biology. Nuclear pore complexes (NPCs) are large cylindrical structures embedded in the nuclear envelope (NE) and the sole communication gates between the nucleus and the cytoplasm. Two pathways of hierarchical assembly of nucleoporins (Nups), the main protein constituents of NPCs, ensure NPC biogenesis at the NE. In cells undergoing open mitosis, a post-mitotic pathway drives Nup assembly onto naked chromatin in the existing NE openings. NPCs can be also formed de novo into enclosed NE during the interphasic pathway, which involves inside-out growth of maturing complexes. Identifying the yet unknown membrane fusogenic factor, or factors, that enable the formation of new pores in the NE may keep scientists busy for some time. But meanwhile, a ground-breaking study from Martin Beck’s team identified a third NPC biogenesis pathway that involves cytoplasmic organelles named annulate lamellae (AL) and biomolecular condensates of Nups (Hampoelz et al. 2019). AL were first described in 1956 by Swift, as groups of parallel membrane sheets present mostly in growing and proliferating cells. As shown previously by the same authors, AL-embedded NPC scaffolds (AL-NPCs) can ‘feed’ the NE pores during early fly embryogenesis. The 2019 study shows that AL-NPCs in the fly egg chamber are formed through liquid–liquid phase separation (LLPS) of specific Nups, and that these Nup granules are transported by microtubules to the sites of AL-NPCs assembly. These findings raise many questions, and as my laboratory enters this new research area, I am intrigued by the possibility that Nup LLPS may have a general role in mammalian NPC biogenesis. Can cytoplasmic Nup granules observed in human cells (Agote-Aran et al. 2020) feed the nuclear pores directly or through AL-like structures? Is the AL presence more common than initially thought? Can the Nup LLPS process contribute to other NPC assembly pathways? Indeed, Nup LLPS was found to stabilize the NPC structure in yeast (Onischenko et al. 2017). Finally, can pathological Nup condensation observed in neurological diseases be prevented by modulating the key LLPS Nups? The study by Hampoelz et al. will surely inspire many scientists.
Martin Beck’s team identified a third NPC biogenesis pathway that involves cytoplasmic organelles named annulate lamellae (AL) and biomolecular condensates of Nups
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