BDNF-induced release of CYFIP1, but not 4E-BP2, from m7GTP cap binding requires MNK1. A, The effect of 30 min BDNF treatment on the binding of 4E-BP2 to an m7GTP cap analog. An unpaired t test revealed an effect of BDNF (t(6) = 3.8, p = 0.009); n = 4. B, The effect of BDNF treatment on CYFIP1 binding to a m7GTP cap analog. An unpaired t test revealed a significant effect of BDNF (t(10) = 7.9, p = 0.01); n = 6. C, Effect of rapamycin on BDNF-induced release of 4E-BP2 from m7GTP binding. A two-way (BDNF × rapamycin) ANOVA revealed a main effect of BDNF (F(1,20) = 13.5, p = 0.002), a main effect of rapamycin (F(1,20) = 119, p < 0.001), and a trend toward an interaction between BDNF and rapamycin administration (F(1,20) = 3.34, p = 0.083); n = 6. D, Effect of MNK-I1 on BDNF-induced release of 4E-BP2 from m7GTP binding. A two-way (BDNF × MNK-I1) ANOVA revealed a main effect of BDNF (F(1,16) = 22, p < 0.001) but no main effect of MNK-I1 (p = 0.43) and no interaction between BDNF and MNK-I1 administration (p = 0.52); n = 5. E, Effect on BDNF-induced release of 4E-BP2 from m7GTP binding in neurons derived from WT, MNK1 or MNK2 KO mice. A 3 × 2 (genotype × BDNF) ANOVA revealed a main effect of BDNF (F(1,30) = 62.8, p < 0.001) an effect of genotype (F(2,30) = 7.32, p = 0.003) but no interaction between BDNF and genotype administration (p = 0.72); n = 6. F, Effect of rapamycin on BDNF-induced release of CYFIP1 from m7GTP binding. A two-way (BDNF × rapamycin) ANOVA revealed a main effect of BDNF (F(1,20) = 5.8, p = 0.025), a main effect of rapamycin (F(1,20) = 7.9, p = 0.011), and an interaction between BDNF and rapamycin administration (F(1,20) = 13.4, p = 0.002); n = 6. G, Effect of MNK-I1 on BDNF-induced release of CYFIP1 from m7GTP binding. A two-way (BDNF × MNK-I1) ANOVA revealed a main effect of BDNF (F(1,16) = 8.8, p = 0.009), a main effect of MNK-I1 (F(1,16) = 82.3, p < 0.001) but no interaction between BDNF and MNK-I1 administration (p = 0.36); n = 5. H, Effect on eIF4E phosphorylation of treating neurons with rapamycin and/or BDNF. A two-way (BDNF × rapamycin) ANOVA revealed a main effect of BDNF (F(1,28) = 9.5, p = 0.005), a main effect of rapamycin (F(1,28) = 11.1, p = 0.002) but no interaction between BDNF and rapamycin administration (p = 0.25); n = 8. I, Effect on BDNF-induced release of CYFIP1 from m7GTP binding in neurons derived from WT, MNK1, or MNK2 KO mice. A 3 × 2 (genotype × BDNF) ANOVA revealed a main effect of BDNF (F(1,30) = 9.63, p = 0.004) a main effect of genotype (F(2,30) = 25.62, p < 0.001), and an interaction between genotype and BDNF (F(2,30) = 3.24, p = 0.05); n = 6; *p < 0.05 compared with NT; +p < 0.05, †p < 0.10 compared with NT within genotype. Error bars represent SEM.