Figure 2. Enhancing eIF2α signaling corrects ΔE Torsin1a mislocalization.
(A) eIF2α signaling pathway diagram. Actions of compounds tested in panels (C) through (F) are indicated in blue.
(B) WGS results relevant to the eIF2α pathway. Blue – gene hits bioinformatically implicating the eIF2α pathway. Red – eIF2α kinases. Dashed lines indicate +/−3SD from mean.
(C-H) Left – Effects of the indicated compounds on Torsin1a localization (black), cell count (grey), and EGFP-Torsin1a expression (green) in the ΔE (C-E, G, H) or WT (F) assay cell lines. Percent Selected Cells was normalized such that vehicle-treated ΔE cells = 100 and vehicle-treated WT cells = 0. GFP Intensity and Cell Count were normalized such that vehicle-treated ΔE cells = 100. Right – Representative images from the respective treatments. Scale bars = 20 μm. n = 4 per compound dose for dose response data or 24 for untreated control data (used for normalization). All data are presented as means ± S.E.M.
