Molecular and genetic basis of the regulation of dopamine transporter

Dopamine transporter (DAT) is a member of the solute carrier (SLC) gene family, such as the Na⁺/Cl^- -dependent transporter subfamily, which participates in the reuptake of released neurotransmitter, thereby controlling the fine-tuning of neurotransmission. DAT as well as noradrenaline transporter and serotonin transporter are associated with psychiatric and neurological disorders, and are targets for antidepressants and drugs of abuse. Recent molecular, pharmacological and genetic approaches to the regulation of DAT have established its importance in the dopaminergic neurotransmission. These studies achieved the identification of intracellular signaling cascades leading to the control of DAT expression, function, trafficking, and degradation. In this chapter, we review the current knowledge about the role of DAT-associated proteins in the regulation of DAT expression and function. In addition, we discuss possible implication of DAT regulation to the vulnerability of dopaminergic neurons to the putative toxicity of certain drugs like amphetamine and factors involved in dopaminergic neurodegeneration. Understanding the molecular and genetic basis of the regulation of DAT is essential for contributing the identification of potential new targets for the treatment of various brain diseases including Parkinson's disease.