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Nucleoporin foci are stress-sensitive condensates dispensable for C. elegans nuclear pore assembly
The EMBO Journal ( IF 11.4 ) Pub Date : 2023-05-31 , DOI: 10.15252/embj.2022112987
Laura Thomas 1 , Basma Taleb Ismail 1 , Peter Askjaer 2 , Geraldine Seydoux 1
Affiliation  

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.

中文翻译:

核孔蛋白焦点是压力敏感的凝聚物,对于秀丽隐杆线虫核孔组装来说是可有可无的

核孔蛋白 (Nups) 组装核孔,形成核质和细胞质之间的渗透性屏障。核孔蛋白还定位于细胞质焦点,被认为充当孔预组装中间体。在这里,我们描述了完整动物秀丽隐杆线虫细胞质 Nup 病灶的组成和发生率。我们发现,在年轻的非应激动物中,Nup 灶仅出现在发育中的精子、卵母细胞和胚胎以及表达高水平核孔蛋白的组织中。焦点是高度内聚的含有 FG 重复序列的核孔蛋白 (FG-Nups) 的缩合物,通过翻译后修饰和伴侣活性将其维持在接近其在细胞质中的溶解度极限。只有一小部分 FG-Nup 分子集中在 Nup 焦点中,其在 M 期溶解并且对于核孔组装来说是可有可无的压力和年龄增长会增强核孔蛋白凝聚,有丝分裂后神经元中单个 FG-Nup 的过度表达足以诱导异位凝聚和机体麻痹。我们推测 Nup 焦点是非必需且具有潜在毒性的凝聚物,其组装在健康细胞中受到积极抑制。
更新日期:2023-05-31
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