Nuclear import receptors are recruited by FG-nucleoporins to rescue hallmarks of TDP-43 proteinopathy.
Bilal KhalilDeepak ChhanganiMelissa C WrenCourtney L SmithJannifer H LeeXingli LiChristian PuttingerChih-Wei TsaiGael FortinDmytro MordererJunli GaoFeilin LiuChun Kim LimJingjiao ChenChing-Chieh ChouCara L CroftAmanda M GleixnerChristopher J DonnellyTodd E GoldeLeonard PetrucelliBjörn OskarssonDennis W DicksonKe ZhangJames ShorterShige H YoshimuraSami J BarmadaDiego E Rincon-LimasWilfried RossollPublished in: Molecular neurodegeneration (2022)
Our findings suggest a novel NLS-independent mechanism where, analogous to its canonical role in dissolving the diffusion barrier formed by FG-Nups in the nuclear pore, KPNB1 is recruited into TDP-43/FG-Nup co-aggregates present in TDP-43 proteinopathies and therapeutically reverses their deleterious phase transition and mislocalization, mitigating neurodegeneration.
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