Fig. 9.

Actin modulates NPC function in C9ORF72-ALS. a Significant rescue of RanGAP1 (black) mislocalization to the NE in MNs expressing the C9ORF72 repeat expansion (G4C2)₈₀ was achieved due to the overexpression of GFP-mDia1 compared to GFP alone (green). b Fibroblasts derived from 3 ALS patients carrying C9ORF72 repeat expansions show increased mislocalization of both RanGAP1 and FG-Nups compared to 3 healthy controls. Treatment of these cells with IMM01 significantly rescued the defects. DMSO was used as vehicle control. c–e Time-lapse images (c), quantification (d) and regression analysis (e) of S-mCherry nuclear import dynamics in cortical neurons expressing GFP or GFP-mDia1 (green) and (G4C2)₈₀. S-mCherry levels are shown as 16-bit heat map. Dashed lines indicate the nucleus. DAPI (blue) was used to detect the nucleus and assess cell health. Scale bars: 10 µm. Bars are mean ± SEM. *p < 0.05, ***p < 0.001. N = 4 (a) and 5 (b, e) independent experiments, and 51–64 cells from 5 independent experiments (c, d). See also Supplementary Figs. 13 and 14 and Supplementary Table 1 for details on statistics