Fig. 3

Impact of 8BrcGMP and p38 MAPK 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 following pretreatments of cells with either 100 µM 8BrcGMP or vehicle for 1 hr. Parallel wells were treated with the PKG inhibitor H8 (10 µM) to validate specificity. B) Altered p38 MAPK-dependent regulation of hSERT in transfected HeLa cells. Cells transfected with hSERT or autism-associated hSERT coding variants were examined for 5-HT transport activities following pretreatments of cells with either 1 µM anisomycin or vehicle for 10 min. Parallel wells were treated with the p38 MAPK inhibitor SB203580 (1 µM) to validate specificity. Results reflect mean values ± SEM of three separate experiments normalized to each mutant’s control measured under vehicle treated conditions (100%). Results in A and B reflect mean values ± SEM of three separate experiments normalized to each mutant’s level under vehicle treated conditions (100%). Data were analyzed by a One-Way ANOVA with post-hoc Bonferonni tests comparing variant to hSERT 8BrcGMP/anisomycin responses with p < 0.05 taken as significant. Figure reproduced from authors’ prior work [79]