Figure 4

DPRs caused TDP-43 mislocalisation to the cytoplasm. (A–D) HeLa cells co-transfected with mCherry-tagged human TDP-43 (red) and GFP-tagged DPR constructs or empty pEGFP-N1 vector as a GFP-only control were fixed and stained 48h post-transfection. TDP-43 was frequently mislocalised to the cytoplasm in cells containing GA, GR or PR inclusions. Many DPR-expressing cells also exhibited some TDP-43 aggregation. Scale bars indicate 15 μm. (E) Graph shows the mean percentage of total TDP-43 fluorescence signal which was localised to the cytoplasm. The proportion of TDP-43 in the cytoplasm was significantly increased by expression of GA1020 (P = 0.0003), GR1136 (P < 0.0011), and PR1100 (P = 0.0349) but not AP1024 (P = 0.9999). n = 3, with a minimum of 30 cells analysed for each independent replicate. Data was analysed by one-way ANOVA with Dunnett’s multiple comparison test. Error bars indicate SEM.