Glutamate is the major excitatory neurotransmitter in the mammalian centralnervous system. After exocytotic release from presynaptic nerve terminals,glutamate diffuses across the synaptic cleft and opens postsynaptic ionotropicglutamate receptors, thus depolarizing the postsynaptic neuron. Synaptic activityis terminated by rapid and efficient uptake into surrounding neurons and glialcells. The function of a glutamatergic synapse thus critically depends on twodistinct transport systems: vesicular and plasma membrane glutamatetransporters. Vesicular glutamate transporters (VGLUTs) accumulate glutamatein synaptic vesicles and determine the amount of released glutamate. Plasmamembrane glutamate transporters (excitatory amino acid transporters, EAATs)clear the synaptic cleft from glutamate, setting the time resolution and energydemand of glutamatergic synaptic signaling. Both classes of glutamatetransporters are not only secondary-active transporters, but also function aschloride channels, with different roles in chloride and glutamate homeostasis.Despite similar transport functions, VGLUTs and EAATs are structurally diverseand employ different molecular mechanisms to overcome the same chemicalchallenges. We here review recent progress in understanding the molecular andcellular biophysics of vesicular glutamate transporters and compare theirproperties with plasma membrane glutamate transporters.
Borghans et al. (Wed,) studied this question.