Ethanol alters endosomal recycling of human dopamine transporters.

The Journal of Biological Chemistry
D Nicole Riherd Methner, R Dayne Mayfield

Abstract

Dynamic membrane trafficking of the monoamine dopamine transporter (DAT) regulates dopaminergic signaling. Various intrinsic and pharmacological modulators can alter this trafficking. Previously we have shown ethanol potentiates in vitro DAT function and increases surface expression. However, the mechanism underlying these changes is unclear. In the present study, we found ethanol directly regulates DAT function by altering endosomal recycling of the transporter. We defined ethanol action on transporter regulation by [(3)H]DA uptake functional analysis combined with biochemical and immunological assays in stably expressing DAT HEK-293 cells. Short-term ethanol exposure potentiated DAT function in a concentration-, but not time-dependent manner. This potentiation was accompanied by a parallel increase in DAT surface expression. Ethanol had no effect on function or surface localization of the ethanol-insensitive mutant (G130T DAT), suggesting a trafficking-dependent mechanism in mediating the ethanol sensitivity of the transporter. The ethanol-induced increase in DAT surface expression occurred without altering the overall size of DAT endosomal recycling pools. We found ethanol increased the DAT membrane insertion rate while havi...Continue Reading

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Citations

Dec 15, 2015·The Journal of Pharmacology and Experimental Therapeutics·Mehrnoosh SooriRobert W Mason
Apr 10, 2017·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Giovanni AddoloratoDaniela Di Giuda
Dec 27, 2016·Frontiers in Neuroscience·Argelia E Rojas-MayorquínDaniel Ortuño-Sahagún

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