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Nat Commun. 2016 Jan 25;7:10423. doi: 10.1038/ncomms10423.

Membrane potential shapes regulation of dopamine transporter trafficking at the plasma membrane.

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Department of Neuroscience, Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, Florida 32610, USA.
Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58203, USA.
Medicinal Chemistry Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA.


The dopaminergic system is essential for cognitive processes, including reward, attention and motor control. In addition to DA release and availability of synaptic DA receptors, timing and magnitude of DA neurotransmission depend on extracellular DA-level regulation by the dopamine transporter (DAT), the membrane expression and trafficking of which are highly dynamic. Data presented here from real-time TIRF (TIRFM) and confocal microscopy coupled with surface biotinylation and electrophysiology suggest that changes in the membrane potential alone, a universal yet dynamic cellular property, rapidly alter trafficking of DAT to and from the surface membrane. Broadly, these findings suggest that cell-surface DAT levels are sensitive to membrane potential changes, which can rapidly drive DAT internalization from and insertion into the cell membrane, thus having an impact on the capacity for DAT to regulate extracellular DA levels.

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