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bioRxiv · 10.1101/2023.03.31.535084

Nucleoporin Nsp1 surveils the phase state of FG-Nups

Otto, T. A.·Bergsma, T.·Dekker, M.·Mouton, S.·Gallardo, P.·Wolters, J. C.·Steen, A.·Onck, P. R.·Veenhoff, L. L.
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Abstract

Transport through the NPC relies on intrinsically disordered FG-Nups forming a selective barrier. Away from the NPC, FG-Nups readily form condensates and aggregates, and we address how this behavior is surveilled in cells. FG-Nups, including Nsp1, together with nuclear transport receptor Kap95, form a native cytosolic condensate in yeast. In aged cells this condensate disappears as cytosolic Nsp1 levels decline. Biochemical assays and modeling show that Nsp1 is a modulator of FG-Nup liquid-liquid phase separation, promoting a liquid-like state. Nsp1s presence in the cytosol and condensates is critical, as a reduction of cytosolic levels in young cells induces NPC assembly and transport defects and a general decline in protein quality control, all quantitatively mimicking aging phenotypes. Excitingly, these phenotypes can be rescued by cytosolic Nsp1. We conclude that Nsp1 is a phase state regulator that surveils FG-Nups and impacts general protein homeostasis. HighlightsO_LINups form native cytosolic condensates C_LIO_LINsp1 reduction mimics NPC aging phenotypes C_LIO_LINsp1 acts as phase state modulator of FG-Nups C_LIO_LINsp1 shares surveillance function with classical chaperones C_LI

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Otto, T. A., Bergsma, T., Dekker, M., Mouton, S., Gallardo, P., Wolters, J. C., Steen, A., Onck, P. R., Veenhoff, L. L.. 2023-03-31. Nucleoporin Nsp1 surveils the phase state of FG-Nups. https://doi.org/10.1101/2023.03.31.535084

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