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Thomas, Laura; Taleb Ismail, Basma; Askjaer, Peter; Seydoux, Geraldine
EMBO journal, 03 July 2023, Letnik: 42, Številka: 13Journal Article
Nucleoporins (Nups) assemble nuclear pores that form the permeability barrier between nucleoplasm and cytoplasm. Nucleoporins also localize in cytoplasmic foci proposed to function as pore pre‐assembly intermediates. Here, we characterize the composition and incidence of cytoplasmic Nup foci in an intact animal, C. elegans. We find that, in young non‐stressed animals, Nup foci only appear in developing sperm, oocytes and embryos, tissues that express high levels of nucleoporins. The foci are condensates of highly cohesive FG repeat‐containing nucleoporins (FG‐Nups), which are maintained near their solubility limit in the cytoplasm by posttranslational modifications and chaperone activity. Only a minor fraction of FG‐Nup molecules concentrate in Nup foci, which dissolve during M phase and are dispensable for nuclear pore assembly. Nucleoporin condensation is enhanced by stress and advancing age, and overexpression of a single FG‐Nup in post‐mitotic neurons is sufficient to induce ectopic condensation and organismal paralysis. We speculate that Nup foci are non‐essential and potentially toxic condensates whose assembly is actively suppressed in healthy cells. Synopsis Highly cohesive, phenylalanine/glycine repeat‐containing nucleoporins (FG‐Nups) form the central channel of nuclear pores and also concentrate in cytoplasmic foci proposed to function as pore pre‐assembly intermediates. This study in the C. elegans model shows that nucleoporin (Nup) foci are transient condensates that are not essential for pore assembly. Cellular Nup foci arise when FG‐Nups accumulate at high levels in the cytoplasm exceeding their solubility limit, such as in oocytes and developing embryos. FG‐Nup solubility is enhanced by posttranslational modifications, including GlcNAcylation and phosphorylation, as well as by chaperone activity. FG‐Nup foci are transient structures that dissolve during M phase, when FG‐Nup solubility increases. FG repeat‐containing nucleoporins form non‐essential, age‐ and stress‐enhanced cytoplasmic condensates in germ cells and developing embryos.
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