Cocaine and antidepressant-sensitive monoamine transporters

In my laboratory, we study cellular regulation of cocaine- and antidepressant-sensitive neurotransmitter transporters. Once secreted into the synapse, extracellular neurotransmitter concentrations must be constrained in order to control the intensity, duration and distribution of signaling. The primary mechanism for terminating neurotransmission is reuptake into presynaptic terminals mediated by neurotransmitter transporter proteins. Transporters specific for monoamines, such as dopamine and norepinephrine, are potently blocked by the psychostimulant drugs cocaine and amphetamines, as well as by therapeutic agents such as antidepressants. These drugs act by blocking reuptake, resulting in increased extracellular monoamine levels.

Recent studies have demonstrated that endogenous cellular mechanisms can also alter transporter function. We are currently using biochemical and cell biological approaches to examine the contribution of membrane trafficking to transporter regulation. Additionally, we are using chimeric proteins and point mutants to investigate structural transporter domains and post-translational modifications involved in the regulatory process. Finally, we are exploring how protein-protein interactions influence transporter function and regulation.