多巴胺重摄取的分子机制

Towards an understanding of molecular mechanisms underlying dopamine reuptake

多巴胺转运体(Dopamine transporter,DAT)位于多巴胺能神经元表面,主要负责将细胞外的多巴胺重摄取至多巴胺能神经元内,控制细胞外多巴胺的浓度,进而影响多巴胺的信号强度和时长。多巴胺转运体与注意力缺陷多动症、抑郁、成瘾等中枢神经系统的功能异常相关。多巴胺转运体的重摄取功能受多种因素的调节,包括底物的浓度、自身位点的翻译后修饰、细胞内蛋白激酶的活性、细胞外的调节信号等。本文就近年来DAT的分子调节机制以及在脑疾病发病机制中作用的研究进展做一综述。

Dopamine transporter （DAT） is normally localized in the cell surface of dopaminergic neurons and is responsible for regulating the concentration of dopamine in extracellular space by reuptaking dopamine into dopaminergic neurons. Dopaminergic neurotransmission is thus fine-turned. This mechanism has significant impact on the strength and duration of extracellular dopamine signals. Dysfunction of DAT has been associated with several brain disorders, such as attention-deficit hyperactivity disorder, depression, drug addiction. Recent reports have demonstrated that several factors, including the concentration of substrate, DAT post-translational modification, protein kinase activities and extracellular signals, contribute to the regulation of DAT function. In this review, we will discuss some of the recent research progress on the molecular mechanisms underlying dopamine reuptake and link changes in DAT trafficking to brain disorders.