Project description:The dopamine transporter facilitates dopamine reuptake from the extracellular space to terminate neurotransmission. The transporter belongs to the neurotransmitter:sodium symporter family, which includes transporters for serotonin, norepinephrine, and GABA that utilize the Na+ gradient to drive the uptake of substrate. Decades ago, it was shown that the serotonin transporter also antiports K+, but investigations of K+-coupled transport in other neurotransmitter:sodium symporters have been inconclusive. Here, we show that ligand binding to the drosophila- and human dopamine transporters are inhibited by K+, and the conformational dynamics of the drosophila dopamine transporter in K+ are divergent from the apo- and Na+-states. Furthermore, we found that K+ increased dopamine uptake by the drosophila dopamine transporter in liposomes, and visualized Na+ and K+ fluxes in single proteoliposomes using fluorescent ion indicators. Our results expand on the fundamentals of dopamine transport and prompt a reevaluation of the impact of K+ on other transporters in this pharmacologically important family.

2022-05-20 | PXD032663 | Pride

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