Regulation of the dopamine transporter by phosphorylation.
Regulation of the dopamine transporter by phosphorylation.
复制标题
通过磷酸化调节多巴胺转运蛋白。
DOI：
10.1007/3-540-29784-7_10
复制
发表时间：
2006
影响因子：
--
通讯作者：
Vaughan,RA
中科院分区：
文献类型：
--
作者：
Foster,JD;Cervinski,MA;Gorentla,BK;Vaughan,RA
多巴胺转运蛋白（DAT）是一种神经元磷蛋白，是精神活性药物的靶点，在通过从突触空间重摄取多巴胺来终止多巴胺能传递中起关键作用。因此，DAT活性和质膜表达的控制是药物作用和突触多巴胺水平的空间和时间调节的中心。DAT以组成性和蛋白激酶C依赖性方式在质膜和内体隔室之间快速运输。激酶激活剂、磷酸酶抑制剂和转运底物调节DAT磷酸化和活性，但磷酸化在这些过程中的潜在机制和作用知之甚少。DAT功能的复杂适应性变化可能与这些过程有关，也可由精神兴奋剂和治疗性转运阻滞剂（如可卡因和哌甲酯）诱导。本章提供了一个关于DAT磷酸化及其与转运蛋白活性和贩运的关系的知识现状的概述。更好地了解多巴胺能神经元如何调节DAT功能和磷酸化的作用，可能会导致识别新的治疗靶点，用于治疗和预防多巴胺能疾病。
The dopamine transporter (DAT) is a neuronal phosphoprotein and target for psychoactive drugs that plays a critical role in terminating dopaminergic transmission by reuptake of dopamine from the synaptic space. Control of DAT activity and plasma membrane expression are therefore central to drug actions and the spatial and temporal regulation of synaptic dopamine levels. DATs rapidly traffic between the plasmamembrane and endosomal compartments in both constitutive and protein kinase C-dependent manners. Kinase activators, phosphatase inhibitors, and transported substrates modulate DAT phosphorylation and activity, but the underlying mechanisms and role of phosphorylation in these processes are poorly understood. Complex adaptive changes in DAT function potentially related to these processes are also induced by psychostimulant and therapeutic transport blockers such as cocaine andmethylphenidate. This chapter provides an overview of the current state of knowledge regarding DAT phosphorylation and its relationship to transporter activity and trafficking. A better understanding of how dopaminergic neurons regulate DAT function and the role of phosphorylation may lead to the identification of novel therapeutic targets for the treatment and prevention of dopaminergic disorders.