Presynaptic regulation of dopamine release: Role of the DAT and VMAT2 transporters

The signaling dynamics of the neurotransmitter dopamine has been established to have an important role in a variety of behavioural processes including motor control, cognition, and emotional processing. Key regulators of transmitter release and the signaling dynamics of dopamine are the plasma membrane reuptake transporter (DAT) and the vesicular monoamine transporter (VMAT2). These proteins serve to remove dopamine molecules from the extracellular and cytosolic space, respectively and both determine the amount of transmitter released from synaptic vesicles. This review provides an overview of how these transporter proteins are involved in molecular regulation and function together to govern the dynamics of vesicular release with opposing effects on the quantal size and extracellular concentration of dopamine. These transporter proteins are both focal points of convergence for a variety of regulatory molecular cascades as well as targets for many pharmacological agents. The ratio between these transporters is argued to be useful as a molecular marker for delineating dopamine functional subsystems that may differ in transmitter release patterns.