Excitatory amino acid transporters

Orexin neurons, likely to be glutamatergic themselves, express the excitatory amino acid transporter EAAT3, vesicular glutamate transporters VGLUT1 and VGLUT2, secretogranin II, ionotropic (NMDAR,... 

HIV proteins can also disrupt ion homeostasis in astrocytes, which compromises neuronal function (Pulliam et al. 1993 Benos et al. 1994a, b Holden et al. 1999). Intact HIV-1 virions or gpl20 also markedly inhibit glutamate uptake by astrocytes and cause reductions in excitatory amino acid transporter-2 (EAAT2) mRNA and protein levels (Wang et al. 2003). The inability of astrocytes to buffer extracellular glutamate is likely to decrease the excitotoxic threshold of bystander neurons. 

Campiani, G., et al. A rational approach to the design of selective substrates and potent nontransport-able inhibitors of the excitatory amino acid transporter EAAC1 (EAAT3). 

Excitotoxicity (see Chs 15 and 32) has been suggested to be a mechanism by which motor neurons are damaged in ALS [25,48,49]. About 60-70% of sporadic ALS patients have a 30-95% reduction in the levels of the astroglial glutamate transporter EAAT2 (excitatory amino acid transporter 2), also termed GLT-1, in motor cortex and spinal cord [25, 48, 49]. Reduction in level of activity of this major glutamate transporter leads to increased extracellular concentrations of glutamate at synapses and evidence of excitotoxicity exists in some patients with ALS. 

EAAT excitatory amino acid transporter GLUT glucose transporter guanosine 5 -monophosphate... 

Fig. 3. Synaptic localization of the mGluRs. The predominant localizations of the seven mGluR subtypes expressed in the CNS. The typical localizations of iGluRs and excitatory amino acid transporters (EAATs) are given, and the regulation of Glu release, iGluR signaling and ion channel activities mediated by the mGluRs is shown.

Wadiche, J. I., Amara, S. G., and Kavanaugh, M. P. (1995) Ion fluxes associated with excitatory amino acid transport. Neuron 15, 721-728. 

Seal, R. P., Leighton, B. H., and Amara, S. G. (2000) A model for the topology of excitatory amino acid transporters determined by the extracellular accessibility of substituted cysteines. Neuron 25,695-706. 

Zerangue, N. and Kavanaugh, M. P. (1996) Interaction of L-cysteine with a human excitatory amino acid transporter. J. Physiol. 493,419—423. 

Arriza, J. L Eliasof, S., Kavanaugh, M. R, and Amara, S. G. (1997) Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc. Natl. Acad. Sci. USA 94,4155-4160. 

Luruta, A., Martin, L. J., Lin, C. L Dykes-Hoberg, M., and Rothstein, J. D. (1997) Cellular and synaptic localization of the neuronal glutamate transporters excitatory amino acid transporter 3 and 4. Neuroscience 81,1031-1042. 

Faure, S., Jensen, A.A., Maurat, V., Gu, X., Sagot, E., Aitken, D.J., Bolte, J., Gefflaut, T. and Bunch, L., Stereoselective chemoenzymatic s3mthesis of the four stereoisomers of l-2-(2-carboxycyclobutyl)glycine and pharmacological characterization at human excitatory amino acid transporter subtypes 1, 2, and 3. J. Med. Chem., 2006, 49, 6532-6538. 

Excitatory amino acid transporters (EAATs) are the primary regulators of extracellular glutamate concentrations in the CNS. Glutamate clearance (and consequently glutamate concentration and diffusion in the extracellular space) is associated with the degree of astrocytic coverage of its neurons (Oliet et al. 

Aiba A, Chen C, Herrup K, et al (1994) Reduced hippocampal long-term potentiation and context-specific deficit in associative learning in mGluRl mutant mice. Cell 79 365-375 Amara SG, Fontana ACK (2002) Excitatory amino acid transporters keeping up with glutamate. Neimochem Int 41 313-318... 

Boehmer C., Rajamanickam J., Schniepp R., Kohler K., Wulff P., Kuhl D., Palmada M., and Lang F. (2005). Regulation of the excitatory amino acid transporter EAAT5 by the serum and glucocorticoid dependent kinases SGK1 and SGK3. Biochem. Biophys. Res. Commun. 329 738-742. 

Chretien F., Le Pavec G., Vallat-Decouvelaere A. V., Delisle M. B., Uro-Coste E., Ironside J. W., Gambetti P., Parchi P., Creminon C., Dormont D., Mikol J., Gray F., and Gras G. (2004). Expression of excitatory amino acid transporter-1 (EAAT-1) in brain macrophages and microglia of patients with prion diseases. J. Neuropathol. Exp. Neurol. 63 1058-1071. 

Dunlop J., Lou Z., Zhang Y., and Mcllvain H. B. (1999). Inducible expression and pharmacology of the human excitatory amino acid transporter 2 subtype of L-glutamate transporter. Br. J. Pharmacol. 128 1485-1490. 

Fairman W. A. and Amara S. G. (1999). Functional diversity of excitatory amino acid transporters ion channel and transport modes. Am. J. Physiol 277 F481-F486. 

Nieoullon A., Canolle B., Masmejean F., Guillet B., Pisano P., and Lortet S. (2006). The neuronal excitatory amino acid transporter EAAC1/EAAT3 does it represent a major actor at the brain excitatory synapse J. Neurochem. 98 1007-1018. 

Pignataro L., Sitaramayya A., Finnemann S. C., and Sarthy V. P (2005). Nonsynaptic localization of the excitatory amino acid transporter 4 in photoreceptors. Mol. Cell Neuiosci. 28 440-451. 

Ward M. M., Jobling A. I., Puthussery T., Foster L. E., and Fletcher E. L. (2004). Localization and expression of the glutamate transporter, excitatory amino acid transporter 4, within astrocytes of the rat retina. Cell Tissue Res. 315 305-310. 

Amara SG, Fontana ACK (2002) Excitatory amino acid transporters keeping up with glutamate. Neurochem Internat 41 313... 

---