Dynamic regulation of the dopamine transporter

In the mammalian central nervous system the dopamine transporter (DAT) is the primary mechanism for clearance of dopamine from the extracellular space. Presynaptic receptors for dopamine and other neurotransmitters (auto-receptors and hetero-receptors) present on dopaminergic neurons are poised to regulate the activity of the dopamine transporter acutely through their actions on intracellular signaling systems. The mechanisms proposed for acute presynaptic regulation of dopamine transport include direct effects of phosphorylation on enzymatic rate, indirect effects through the alteration of the electrical and chemical gradients that drive transport and/or the modulation of transporter number through the trafficking of carriers to and from the cell surface. This review focuses on recent evidence for several distinct mechanisms which dynamically regulate dopamine transporter activity and thus have an important role in shaping the duration and amplitude of dopamine signals in the brain.