Association with serotonin transporter enables the phosphorylation of insulin receptor in placenta.

Upon binding to insulin, the β-subunit of insulin receptor (IR) is phosphorylated and instantly activates intracellular signaling. A defect in this process causes the development of several metabolic disorders including non-insulin-dependent diabetes, such as type 2 and gestational diabetes mellitus (GDM). Under diabetic conditions the phosphorylation of IR in placenta, but not in platelets, is impaired. Interestingly the cellular distribution of the serotonin transporter (SERT), which utilizes the insulin signaling for posttranslational modification, shows tissue-type-dependent variation: SERT function is impaired in GDM-associated placenta, but not in platelets. In order to understand the correlation between IR, SERT and their tissue-type-dependent features, we tested an association between SERT and IR and whether this association affects the phosphorylation of IR. Using various approaches, we demonstrated a physical association between the Carboxyl terminal of SERT and the β-subunit of IR. This association was found on the plasma membrane of the placenta and the platelets. Next, the contribution of the SERT-IR association to the phosphorylation of IR was analyzed in heterologous and endogenous expression systems following insulin-treatment. The

Déclaration de conflit d'intérêts

CONFLICT OF INTEREST STATEMENT The authors declare no competing interests that might be perceived to influence the results and/or discussion reported in this paper.