Molecular and functional characterization of vesicular glutamate and GABA transporters.

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Synaptic vesicles contain specific transporters (VGLUTs, VGAT) that accumulate the neurotransmitters glutamate and GABA depending on a V-ATPase-driven electrochemical proton gradient. Previously we found that VGLUTs contains two anion and one cation binding sites, allowing for the transporter to adjust to the changing ionic conditions during vesicle filling. In the present application, we aim to analyze the inherent sodium/phosphate transporter activity of VGLUT and the impact of phosphate on glutamate uptake. Furthermore, we will analyze the effects of ketone bodies and lithium on the mechanism of glutamate uptake since previous publications and own results suggest that VGLUT may represent a target for clinically relevant metabolic changes or psychiatric drugs. Finally, we will capitalize on the tools developed for the study of VGLUT such as reconstitution of purified proteins in liposomes with external proton pumps to clarify the controversially discussed ionic requirements for vesicular GABA transport.