Fig. 1

KPNB1 and other nuclear import receptors (NIRs) reduce the pathological aggregation of TDP-CTF. a Immunofluorescence of SH-SY5Y human neuroblastoma cells co-expressing mCherry or mCherry-TDP-CTF with GFP or one of 27 GFP-tagged α-importins, β-importins, and exportins. Based on this microscopy screen, transport proteins were divided in four categories according to their activity towards TDP-CTF aggregates: “no effect on aggregation”, “co-aggregation”, “reduced aggregation” (=transport proteins that only reduce the size of TDP-CTF aggregates), and “abolished aggregation” which includes most β-importins. Arrowheads indicate co-aggregation. Hoechst staining was used to outline nuclei. Scale bar: 5 μm. b Western blot analysis and quantification of insoluble mCherry-TDP-CTF protein levels in SH-SY5Y cells expressing GFP or one of each 27 GFP-tagged α-importins, β-importins, and exportins. Several β-importin family NIRs significantly reduced insoluble TDP-CTF levels, including KPNB1, IPO3/TNPO2, IPO4, IPO9, and IPO13. KPNB1 (in bold) was used as a reference. β-tubulin was used as a loading control. Statistical analysis was performed using one-way ANOVA and Bonferroni’s post hoc test (*p < 0.05, **p < 0.01, ***p < 0.001, n = 3)