Role of the E3 ubiquitin ligase HRD1 in the regulation of serotonin transporter function

To elucidate the regulation of serotonin transporter (SERT) function via its membrane trafficking, we investigated involvement ubiquitin E3 ligase HRD1 (HMG-CoA reductase degradation protein), which participates in endoplasmic reticulum (ER)-associated (ERAD), functional SERT. Cells transiently expressing wild-type SERT or a C-terminal deletion mutant (SERTΔCT), protein predicted to be misfolded, were used for experiments. Studies using HRD1-overexpressing HRD1-knockdown cells demonstrated that is involved proteolysis. Overexpression promoted ubiquitination, effect was augmented by treatment with proteasome inhibitor MG132. Immunoprecipitation studies revealed interacts presence In addition, intracellularly colocalized SERT, especially aggregates SERTΔCT ER. also affected uptake activity accordance expression levels protein. These results suggest contributes trafficking and through ERAD-mediated degradation.