Fig 3. CG-dependent reduction of PrP^C levels relies predominantly on endo/lysosomal degradation pathway.

(A,B) Inhibition of calpain proteases with A6185 or calpastatin did not rescue the ouabain-dependent reduction in steady-state ATP1A1 or PrP^C levels in ReN VM cells. (C,D) Proteasomal inhibition with MG132 or lactacystin caused an increase in steady-state ATP1A1 levels yet did not rescue the reduction in PrP^C levels that is observed in ouabain-treated cells. (E,F) In contrast, inhibition of endo/lysosomal degradation pathways with bafilomycin A1 or E64D blocked the ouabain-dependent PrP^C reduction. Quantitative graphs in this figure depict the means of signal intensities and their standard deviations. Asterisks reflect significance thresholds with one asterisk shown if t-tests returned p<0.05 and two asterisks indicating p<0.005.