Figure 2.
Chronic in vivo administration of PF-4708671 and FS-115 differentially affects the phosphorylation of translation control molecules. (a and b) Chronic treatment of WT and Fmr1 KO mice with PF-4708671 significantly alters eEF2 phosphorylation, but not S6 phosphorylation, in a genotype-specific manner. n=5 mice per genotype per treatment; *p<0.05 with two-way ANOVA (genotype x treatment), followed by Tukey's post hoc test. Significant interaction effect was found: F(3,19)=5.87, Fcrit=4.49. (c and d) Five-day treatment of WT and Fmr1 KO mice with FS-115 significantly decreased S6 phosphorylation and increased eEF2 phosphorylation. n=6–9 mice per genotype per treatment; *p<0.05 and ***p<0.001 with two-way ANOVA (genotype x treatment), followed by Tukey's post hoc test. For both pS6 and eEF2, significant effect of interaction was found: F(3,23)=5.008, Fcrit=4.35 for pS6; F(3,32)=9.508, Fcrit=4.14. (e and f) BONCAT AHA incorporation in cortical lysates of mice treated with vehicle, PF-4708671 or FS-115. n=4 mice per genotype per treatment. *p<0.05 and **p<0.01 by two-way ANOVA (genotype x treatment), followed by Bonferroni's post hoc test. Significant interaction effect was obtained F(3,15)=5.811, Fcrit=5.31. Error bars represent SEM in (b), (d), and (f). See also Supplementary Figure S2 for eIF4B phosphorylation levels with acute treatment of PF-4708671 and FS-115.