Figure 4.
Impact of PKC and PP2A on SERT activity of autism-associated hSERT-coding variants. (a) Activity modulation. HeLa cells transfected with hSERT or autism-associated hSERT-coding variants were examined for 5-HT transport activities as described in §2 following pretreatments of cells with either vehicle or 0.1 or 1 μM β-PMA for 30 min. Parallel wells were treated with the PKC inhibitors staurosporine (stauro; 10 μM) or bisindolylmaleimide (BIM, 10 μM). Altered PP2A-dependent regulation of hSERT in transfected HeLa cells. (c) The cells transfected with hSERT or autism-associated hSERT-coding variants were examined for 5-HT transport activities as described in §2 following pretreatments of cells with increasing concentrations of (b) calyculin A or (c) fostriecin for 10 min. Results reflect mean±s.e.m. of three separate experiments normalized to each mutant's control measured under vehicle-treated conditions (100%). Results in (a–c) reflect mean±s.e.m. of three separate experiments normalized to each mutant's level under vehicle-treated conditions (100%). Data were analysed by a one-way ANOVA with post hoc Bonferroni tests comparing the variant with hSERT responses, with *p<0.05 taken as significant.