Glutamate transporters neuron-specific

Roseth S, Fykse EM, Fonnum F (1995) Uptake of L-glutamate into rat brain synaptic vesicles effect of inhibitors that bind specifically to the glutamate transporter. J Neurochem 65 96-103 Ryan TA (1996) Endocytosis at nerve terminals timing is everything. Neuron 17 1035-7 Ryan TA, Smith SJ (1995) Vesicle pool mobilization during action potential firing at hippocampal synapses. Neuron 14 983-9... 

Northington FJ, Traystman RJ, Koehler RC, Martin LJ (1999) GLTl, glial glutamate transporter, is transiently expressed in neurons and develops astrocyte specificity only after midgestation in the ovine fetal brain. J... 

Harkany, T., Hartig, W., Berghuis, R, et al. (2003) Complementary distribution of type 1 cannabinoid receptors and vesicular glutamate transporter 3 in basal forebrain suggests input-specific retrograde signaling by cholinergic neurons. Eur. J. Neurosci. 18 (7), 1979-1992. 

If a substance is to be a NT it should be possible to demonstrate appropriate enzymes for its synthesis from a precursor at its site of action, although peptides are transported to their sites of location and action after synthesis in the axon or distal neuronal cell body. The specificity of any enzyme system must also be established, especially if they are to be modified to manipulate the levels of a particular NT, or used as markers for it. Thus choline acetyltransferase (ChAT) may be taken as indicative of ACh and glutamic acid decarboxylase (GAD) of GABA but some of the synthesising enzymes for the monoamines lack such specificity. 

The neurotransmitter phenotype, (i.e., what type of neurotransmitter is stored and ultimately will be released from the synaptic bouton) is determined by the identity of the neurotransmitter transporter that resides on the synaptic vesicle membrane. Although some exceptions to the rule may exist all synaptic vesicles of a given neuron normally will express only one transporter type and thus will have a dehned neurotransmitter phenotype (this concept is enveloped in what is known as Dale s principle see also Reference 19). To date, four major vesicular transporter systems have been characterized that support synaptic vesicle uptake of glutamate (VGLUT 1-3), GABA and glycine (VGAT), acetylcholine (VAChT), and monoamines such as dopamine, norepinephrine, and serotonin (VMAT 1 and 2). Vesicles that store and release neuropeptides do not have specific transporters to load and concentrate the peptides but, instead, are formed with the peptides already contained within. 

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]. 

---