||University of Massachusetts
Howard Hughes Medical
Department of Biochemistry
Emory University, Atlanta, GA
|Harvard Medical School
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.