Figure 5.

p38 and JNK inhibitors do not rescue post‐Golgi trafficking of ATP7A mutants. HeLa cells were transfected with either ATP7A^WT (A), ATP7A^A1362D (B), or ATP7A^L873R (C) mutant. Then, cells were exposed to a 200 μM treatment with BCS (‐Cu) and fixed directly or incubated with 100 μM CuSO₄ for an additional 2 hours (+Cu). p38 or JNK inhibitors were added (as indicated in B and C) for 24 hours prior to fixation. Fixed cells were labeled for TGN46 and visualized under a confocal microscope. (A) ATP7A^WT moved from the Golgi (top panel) to the PM (bottom panel) after Cu increase. (B) ATP7B^A1362D mutant remained associated with TGN46 under both low‐Cu and high‐Cu conditions (left column). Neither p38 nor JNK inhibitors allowed the mutant to be transported from the Golgi to the PM in response to increasing Cu (middle and right columns). (C) The ATP7A^L873R mutant remained distributed over the PM, independently of the Cu levels (left column). Incubation with p38 or JNK inhibitors did not correct the mutant from the PM to the Golgi (middle and right columns), even when Cu levels were low (top row). Scale bar = 4.8 μm (A‐C). Abbreviation: inh, inhibitor.