Fig. 8

A model for a novel role of KPNB1 and other NIRs as molecular chaperones for FG-Nup-containing assemblies. a KPNB1 facilitates nuclear transport by disengaging hydrophobic interactions between FG-repeats that form the hydrogel barrier within nuclear pore complexes. b KPNB1 prevents detrimental phase transition of FG-Nups and other aggregation-prone proteins that form cytoplasmic foci under cellular crowding conditions. c, KPNB1 is recruited into pathological FG-Nups and TDP-43 co-aggregates in an NLS-independent manner, counters their aberrant phase transition, and relocates TDP-43 into the nucleus. Similar mechanisms may apply to other NIRs. IDR: intrinsically disordered region; RRM: RNA-recognition motif; PrLD: prion-like domain. (Created with BioRender.com)