The mechanism and regulation of vesicular glutamate transport: Coordination with the synaptic vesicle cycle

Abstract The transport of classical neurotransmitters into synaptic vesicles generally relies on a H+ electrochemical gradient (∆μH+). Synaptic vesicle uptake of glutamate depends primarily on the electrical component ∆ψ as the driving force, rather than the chemical component ∆pH. However, the vesicular glutamate transporters (VGLUTs) belong to the solute carrier 17 (SLC17) family, which includes closely related members that function as H+ cotransporters. Recent work has also shown that the VGLUTs undergo allosteric regulation by H+ and Cl−, and exhibit an associated Cl− conductance. These properties appear to coordinate VGLUT activity with the large ionic shifts that accompany the rapid recycling of synaptic vesicles driven by neural activity. Recent structural information also suggests common mechanisms that underlie the apparently divergent function of SLC17 family members, and that confer allosteric regulation.