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bioRxiv · 10.1101/2022.08.22.504855

Multiple mechanisms prevent ectopic condensation of FG nucleoporins in the cytoplasm

Thomas, L.·Askjaer, P.·Seydoux, G.
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Abstract

Nucleoporins (Nups) assemble nuclear pores that form the permeability barrier that separates nucleoplasm from cytoplasm. Nups have also been observed 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 Nup levels. The foci are condensates of highly cohesive FG-Nups that 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. Nup 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. Our results suggest that Nup foci are non-essential, "accidental", and potentially toxic condensates whose assembly is actively suppressed in healthy cells.

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Thomas, L., Askjaer, P., Seydoux, G.. 2022-08-22. Multiple mechanisms prevent ectopic condensation of FG nucleoporins in the cytoplasm. https://doi.org/10.1101/2022.08.22.504855

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