Besada Christina, Mortensen Ole Valente
Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, USA.
Adv Neurobiol. 2025;46:95-119. doi: 10.1007/978-3-031-96364-3_4.
The dopamine transporter (DAT) is a plasma membrane protein expressed in dopamine (DA) neurons of the central nervous system and is critical for regulating DA neurotransmission. The DAT is responsible for the reuptake of released DA back into the presynaptic neuron, resulting in the termination of DA transmission. This process also recycles the DA back into the dopaminergic neuron for subsequent release. DAT is the target of psychostimulants including cocaine and amphetamines and has been associated with several neuropsychiatric disorders. Only DAT proteins located on the plasma membrane can remove DA from the extracellular space, and the number of DAT proteins on the cell-surface therefore determines the efficiency of DA clearance. As a result, regulating DAT surface expression is a critical means to regulating the magnitude and duration of DA neurotransmission. This chapter will discuss the different processes and proteins that have been shown to affect DAT surface expression and discuss the relevance to normal DA physiology and diseases that involve aberrant DA signaling.
多巴胺转运体(DAT)是一种在中枢神经系统多巴胺(DA)神经元中表达的质膜蛋白,对调节DA神经传递至关重要。DAT负责将释放的DA重新摄取回突触前神经元,从而终止DA传递。这一过程还将DA循环回多巴胺能神经元以便随后释放。DAT是包括可卡因和苯丙胺在内的精神兴奋剂的作用靶点,并且与多种神经精神疾病有关。只有位于质膜上的DAT蛋白才能从细胞外空间清除DA,因此细胞表面DAT蛋白的数量决定了DA清除的效率。因此,调节DAT表面表达是调节DA神经传递的幅度和持续时间的关键手段。本章将讨论已被证明影响DAT表面表达的不同过程和蛋白,并讨论其与正常DA生理学以及涉及异常DA信号传导的疾病的相关性。