Chapter

Neurotransmitter Transporters

Volume 175 of the series Handbook of Experimental Pharmacology pp 197-214

Regulation of the Dopamine Transporter by Phosphorylation

  • J. D. FosterAffiliated withDepartment of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences
  • , M. A. CervinskiAffiliated withDepartment of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences
  • , B. K. GorentlaAffiliated withDepartment of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences
  • , R. A. VaughanAffiliated withDepartment of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences

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Abstract

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.

Keywords

Dopamine transporter Phosphorylation Protein kinase C Methamphetamine Cocaine