Brain vesicular glutamate transporters

Danik M., Cassoly E., Manseau F., Sotty F., Mouginot D., and Williams S. (2005). Frequent coexpression of the vesicular glutamate transporter 1 and 2 genes, as well as coexpression with genes for choline acetyltransferase or glutamic acid decarboxylase in neurons of rat brain. J. Neurosci. Res. 81 506-521. 

Stensrud MJ, Chaudhry FA, Leergaard TB et al (2013) Vesicular glutamate transporter-3 in the rodent brain vesicular colocalization with vesicular y-aminobutyric acid transporter. J Comp Neurol 521 3042-3056... 

Synaptic vesicles isolated from brain exhibit four distinct vesicular neurotransmitter transport activities one for monoamines, a second for acetylcholine, a third for the inhibitory neurotransmitters GABA and glycine, and a fourth for glutamate [1], Unlike Na+-dependent plasma membrane transporters, the vesicular activities couple to a proton electrochemical gradient (A. lh+) across the vesicle membrane generated by the vacuolar H+-ATPase ( vacuolar type proton translocating ATPase). Although all of the vesicular transport systems rely on ApH+, the relative dependence on the chemical and electrical components varies (Fig. 1). The... 

The exocytotic release of neurotransmitters from synaptic vesicles underlies most information processing by the brain. Since classical neurotransmitters including monoamines, acetylcholine, GABA, and glutamate are synthesized in the cytoplasm, a mechanism is required for their accumulation in synaptic vesicles. Vesicular transporters are multitransmembrane domain proteins that mediate this process by coupling the movement of neurotransmitters to the proton electrochemical gradient across the vesicle membrane. 

Cu is normally found at relatively high levels in the brain (100-150 xM) with substantial variations at the cellular and subcellular level [55-57]. Ionic Cu is compartmentalized into a post-synaptic vesicle and released upon activation of the NMDA-R but not AMPA/kainate-type glutamate receptors [58]. The Menkes Cu7aATPase is the vesicular membrane Cu transporter, and upon NMDA-R activation, it traffics rapidly and reversibly to neuronal processes, independent of the intracellular Cu concentration [58]. Cu ions function to suppress NMDA activation and prevent excitotoxicity by catalyzing S-nitrosylation of specific cysteine residues on the extracellular domain of the NRl and NR2A subunits of the NMDA receptor [58]. The concentrations of Cu in the synaptic cleft can reach approximately 15 xM. Subsequently, Cu is cleared by uptake mechanisms from the synaptic cleft. Several studies have shown that Cu levels increase with age in the brains of mice [22-24]. 

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