@article{17775ca9c9f94ac69ecbb168da5b51a7,
title = "Nucleoporin foci are stress-sensitive condensates dispensable for C. elegans nuclear pore assembly",
abstract = "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.",
keywords = "C. elegans, aging, condensate, nucleoporin, oocyte",
author = "Laura Thomas and {Taleb Ismail}, Basma and Peter Askjaer and Geraldine Seydoux",
note = "Funding Information: We thank all members of the Seydoux and Cochella Labs, Orna Cohen‐Fix, and the Baltimore Worm Club for support and many helpful discussions. We thank Cristina Ayuso and Skyler Lemmon for assistance with genome engineering, Madeline Cassani for generating strain JH3656, and the Fromme Lab for generously sharing yeast strains and plasmids. We thank the Chuang Lab for sharing the transportin::mNeonGreen strain and the Greenstein Lab for sharing the GFP::NDC1 strain. Several strains were provided by the Caenorhabditis Genetics Center (CGC), which is supported by the National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440). This work was funded by the Agencia Estatal de Investigaci{\'o}n (PID2019‐105069GB‐I00) and the National Institutes of Health (R37HD037047). LT is a postdoctoral fellow of the Life Sciences Research Foundation supported by the Howard Hughes Medical Institute. GS is an investigator of the Howard Hughes Medical Institute. C. elegans C. elegans Funding Information: We thank all members of the Seydoux and Cochella Labs, Orna Cohen-Fix, and the Baltimore Worm Club for support and many helpful discussions. We thank Cristina Ayuso and Skyler Lemmon for assistance with C. elegans genome engineering, Madeline Cassani for generating strain JH3656, and the Fromme Lab for generously sharing yeast strains and plasmids. We thank the Chuang Lab for sharing the transportin::mNeonGreen strain and the Greenstein Lab for sharing the GFP::NDC1 strain. Several C. elegans strains were provided by the Caenorhabditis Genetics Center (CGC), which is supported by the National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440). This work was funded by the Agencia Estatal de Investigaci{\'o}n (PID2019-105069GB-I00) and the National Institutes of Health (R37HD037047). LT is a postdoctoral fellow of the Life Sciences Research Foundation supported by the Howard Hughes Medical Institute. GS is an investigator of the Howard Hughes Medical Institute. Publisher Copyright: {\textcopyright} 2023 The Authors. Published under the terms of the CC BY 4.0 license.",
year = "2023",
month = jul,
day = "3",
doi = "10.15252/embj.2022112987",
language = "English (US)",
volume = "42",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "EMBO Press",
number = "13",
}