Figure 4
IL6-induced STAT3 signaling exerts a regulatory constraint on SERT expression, function and depression-like behavior in the mouse.
Depicted is a schematic model explaining how STAT3 could mediate IL6-dependent regulation of serotonin transporter expression and depression-like behavior in mice. In this model, IL6 initiates its signaling through binding to IL6 receptor (IL6R), which activates downstream protein kinases including tyrosine kinase 2 (TyK2) and janus kinase 1/2 (JAK1/2), leading to the activation of STAT3 signaling through phosphorylation. Phosphorylated STAT3 translocates from the cytosol into the nucleus and binds to the conserved motif TTN5AA on the promoter region of the mouse SERT gene hereby regulating SERT transcription. Altered SERT expression level may contribute to the modulation of depression-like behavior in mice.
