The nature of the binding between insulin receptor and serotonin transporter in placenta (review)

The interplay between the insulin receptor (IR) and serotonin transporter (SERT) allows reciprocal regulation of each other's physiological roles to ensure appropriate responses to specific environmental and developmental signals. The studies reported herein provided substantial evidence of how insulin signaling influences the modification and trafficking of SERT to the plasma membrane via enabling its association with specific endoplasmic reticulum (ER) proteins. While insulin signaling is important for the modifications of SERT proteins, the fact that phosphorylation of IR was significantly down-regulated in the placenta of SERT knock out (KO) mice suggests that SERT also regulates IR. Further suggestive of SERT functional regulation of IR, SERT-KO mice developed obesity and glucose intolerance with symptoms similar to those of type 2 diabetes. The picture emerging from those studies proposes that the interplay between IR and SERT maintains conditions supportive of IR phosphorylation and regulates insulin signaling in placenta which ultimately enables the trafficking of SERT to the plasma membrane. IR-SERT association thus appears to play a protective metabolic role in placenta and is impaired under diabetic conditions. This review focuses on recent findings describing the functional and physical associations between IR and SERT in placental cells, and the dysregulation of this process in diabetes.