Figure 6. p38α MAPK is required for social defeat stress induced cell surface SERT trafficking.

(A) Representative immunoblot of total SERT levels in the different mouse lines used in this study. Data show both species of SERT (75 and 98 kDa) are present in these strains and the absence of SERT-ir in the Slc6a4 knockout (SERT-KO) mouse. Actin-ir was used to control for protein loading. (B). Representative immunoblot of surface SERT expression in biotinylated synaptosomes isolated from unstressed mice (no stress), from mice after SDS, and from mice pretreated with norBNI (10 mg/kg) 24 hr prior to SDS. (Anti-streptavidin-ir confirms equal protein loading after biotinylation and pull down. (C) Quantification of SERT-ir surface expression following SDS of saline-treated wild type, norBNI-treated wild type, and p38αCKO^ePet mice. (* p < 0.05, ** p< 0,01, *** P< 0.001, ANOVA, Bonferroni post-hoc) (D). Quantification of SERT-ir surface expression following U50,488 treatment of wild type and p38α CKO^ePet mice. (*p < 0.05, t-test). n= 8–10 in replicate, and each was taken from a separate animal (E) Cartoon model depicting p38α MAPK dependent SERT translocation and decreased extracellular 5HT. See also Figure S5.