Figure 8

Altering ERAD influences the size of mutant VAPB inclusions. A-D) Incubation of GFP and Myc-VAPB-P56S transfected primary cultured hippocampal neurons with MG132 to inhibit proteasome (B), or BAP31 shRNA construct to down regulate BAP31 expression (C) result in increased size of mutant VAPB inclusions as compared to untreated cultures (A). The relative frequencies of small (< 50 pixels) and large (>200 pixels) were reduced and increased, respectively, by MG132 and BAP31 shRNA treatment (D). * and ***, P < 0.05 and <0.0001 compared to control; one-way ANOVA, Tukey’s post-test. E-G) TEB4 shRNA reduces size and number of mutant VAPB inclusions in cultured hippocampal neurons, also resulting in a reduction of the proportion of cytosol occupied by inclusions in TEB4-shRNA treated cells (G). *, P < 0.05 compared to control (Student’s t-test). Scale bar, 10 μm.