15451
Modulation of the Serotonin Transporter By Interaction with N-Ethylmaleimide-Sensitive Factor
Objectives: In this study, we sought to identify novel SERT-interacting proteins and investigate whether one of such protein regulates SERT function.
Methods: Novel SERT-binding proteins were examined by a pull-down system. Alterations of SERT function and membrane expression upon knockdown of the novel SERT-binding protein were studied in HEK293-hSERT cells. Endogenous interaction of SERT with the protein was evaluated in mouse brains.
Results: N-ethylmaleimide-sensitive factor (NSF) was identified as a novel SERT-binding protein. NSF co-localized with SERT at the plasma membrane, and NSF knockdown resulted in decreased SERT expression at the cell membranes and its uptake function. NSF endogenously co-localized with SERT and interacted with SERT.
Conclusions: It has been reported that NSF interacts with some neurotransmitter receptors, such as glutamate, adrenaline, and dopamine receptors, and regulate membrane trafficking of these receptors. Since it has been reported that many of these receptors are abnormal in autism, it is possible that NSF plays a key role in the pathophysiology of the disorder.