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Gene Review

SLC1A2  -  solute carrier family 1 (glial high...

Homo sapiens

Synonyms: EAAT2, Excitatory amino acid transporter 2, GLT-1, GLT1, Glutamate/aspartate transporter II, ...
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Disease relevance of SLC1A2


Psychiatry related information on SLC1A2


High impact information on SLC1A2


Chemical compound and disease context of SLC1A2


Biological context of SLC1A2


Anatomical context of SLC1A2


Associations of SLC1A2 with chemical compounds

  • The glutamate transporter gene, EAAT2/GLT-1, is induced by epidermal growth factor (EGF) and downregulated by tumor necrosis factor alpha (TNFalpha) [24].
  • The EAAT2 subtype was distinguishable from the EAAT1/EAAT3 subtypes by the potency of several inhibitors, but most notably by sensitivity to kainic acid (KA) and dihydrokainic acid (DHK) [25].
  • With regard to the human excitatory amino acid transporter-2 (EAAT2), the inhibitory effect of DL-TBOA (Ki = 5.7 microM) was much more potent than that of dihydrokainate (Ki = 79 microM), which is well known as a selective blocker of this subtype [21].
  • In contrast, a significant effect of diazepam on EAAT2-mediated uptake was only observed at 1000 micromol/l where uptake was inhibited by 60% [26].
  • Here we used cysteine-scanning mutagenesis of the GLT-1 transporter to test the idea that this loop undergoes conformational changes following sodium and substrate binding [27].

Regulatory relationships of SLC1A2

  • Post-translational regulation of EAAT2 function by co-expressed ubiquitin ligase Nedd4-2 is impacted by SGK kinases [28].
  • However, even in the absence of L-glutamate, the membrane conductance of oocytes expressing EAAT1 was significantly increased relative to oocytes expressing EAAT2 or control oocytes [29].
  • Treatment with dibutyryl-cAMP, epidermal growth factor (EGF) or other growth factors both induces expression of GLT-1 and increases expression of GLAST in astrocyte cultures [30].
  • Consequently, a significant increase in CA1 neuronal damage was observed in slices over-expressing EAAT2 in neurons following an acute exposure to exogenous glutamate [31].

Other interactions of SLC1A2

  • Positive and negative regulation of EAAT2 by NF-kappaB: a role for N-myc in TNFalpha-controlled repression [24].
  • KA and DHK potently inhibited EAAT2 transport, but did not significantly affect transport by EAAT1/EAAT3 [25].
  • Herein, we demonstrate that both TNFalpha-mediated repression and EGF-mediated activation of EAAT2 expression require NF-kappaB [24].
  • Furthermore, TNFalpha can abrogate IKKbeta- and p65-mediated activation of EAAT2 [24].
  • The results indicate an upregulation of EAAT2 protein expression in CA1 and CA2 in neurones in the non-HS group [32].

Analytical, diagnostic and therapeutic context of SLC1A2


  1. The glutamate and neutral amino acid transporter family: physiological and pharmacological implications. Kanai, Y., Hediger, M.A. Eur. J. Pharmacol. (2003) [Pubmed]
  2. Reduced expression of glutamate transporter EAAT2 and impaired glutamate transport in human primary astrocytes exposed to HIV-1 or gp120. Wang, Z., Pekarskaya, O., Bencheikh, M., Chao, W., Gelbard, H.A., Ghorpade, A., Rothstein, J.D., Volsky, D.J. Virology (2003) [Pubmed]
  3. Decreased expression of glutamate transporters in astrocytes after human traumatic brain injury. Landeghem, F.K., Weiss, T., Oehmichen, M., Deimling, A.V. J. Neurotrauma (2006) [Pubmed]
  4. Insights into glutamate transport regulation in human astrocytes: cloning of the promoter for excitatory amino acid transporter 2 (EAAT2). Su, Z.Z., Leszczyniecka, M., Kang, D.C., Sarkar, D., Chao, W., Volsky, D.J., Fisher, P.B. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  5. Alternative splicing of glutamate transporter EAAT2 RNA in neocortex and hippocampus of temporal lobe epilepsy patients. Hoogland, G., van Oort, R.J., Proper, E.A., Jansen, G.H., van Rijen, P.C., van Veelen, C.W., van Nieuwenhuizen, O., Troost, D., de Graan, P.N. Epilepsy Res. (2004) [Pubmed]
  6. EAAT2 regulation and splicing: relevance to psychiatric and neurological disorders. Lauriat, T.L., McInnes, L.A. Mol. Psychiatry (2007) [Pubmed]
  7. Excitatory amino acid transporter EAAT-2 in tangle-bearing neurons in Alzheimer's disease. Thai, D.R. Brain Pathol. (2002) [Pubmed]
  8. Involvement of glial glutamate transporters in morphine dependence. Nakagawa, T., Satoh, M. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  9. Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1. Kang, D.C., Su, Z.Z., Sarkar, D., Emdad, L., Volsky, D.J., Fisher, P.B. Gene (2005) [Pubmed]
  10. Genetic variation of the glutamate transporter EAAT2 gene and vulnerability to alcohol dependence. Sander, T., Ostapowicz, A., Samochowiec, J., Smolka, M., Winterer, G., Schmidt, L.G. Psychiatr. Genet. (2000) [Pubmed]
  11. A polymorphism in the EAAT2 promoter is associated with higher glutamate concentrations and higher frequency of progressing stroke. Mallolas, J., Hurtado, O., Castellanos, M., Blanco, M., Sobrino, T., Serena, J., Vivancos, J., Castillo, J., Lizasoain, I., Moro, M.A., Dávalos, A. J. Exp. Med. (2006) [Pubmed]
  12. SOD1 mutants linked to amyotrophic lateral sclerosis selectively inactivate a glial glutamate transporter. Trotti, D., Rolfs, A., Danbolt, N.C., Brown, R.H., Hediger, M.A. Nat. Neurosci. (1999) [Pubmed]
  13. Aberrant RNA processing in a neurodegenerative disease: the cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis. Lin, C.L., Bristol, L.A., Jin, L., Dykes-Hoberg, M., Crawford, T., Clawson, L., Rothstein, J.D. Neuron (1998) [Pubmed]
  14. ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Bruijn, L.I., Becher, M.W., Lee, M.K., Anderson, K.L., Jenkins, N.A., Copeland, N.G., Sisodia, S.S., Rothstein, J.D., Borchelt, D.R., Price, D.L., Cleveland, D.W. Neuron (1997) [Pubmed]
  15. Altered expression of glutamate transporters under hypoxic conditions in vitro. Hsu, L., Rockenstein, E., Mallory, M., Hashimoto, M., Masliah, E. J. Neurosci. Res. (2001) [Pubmed]
  16. Effects of mild versus deep hypothermia on a cloned human brain glutamate transporter (GLT-1) expressed in Chinese hamster ovary cells. Sakai, F., Amaha, K. Journal of neurosurgical anesthesiology. (2000) [Pubmed]
  17. Intron 7 retention and exon 9 skipping EAAT2 mRNA variants are not associated with amyotrophic lateral sclerosis. Flowers, J.M., Powell, J.F., Leigh, P.N., Andersen, P., Shaw, C.E. Ann. Neurol. (2001) [Pubmed]
  18. The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects. Kanai, Y., Hediger, M.A. Pflugers Arch. (2004) [Pubmed]
  19. Stereoselective Chemoenzymatic Synthesis of the Four Stereoisomers of l-2-(2-Carboxycyclobutyl)glycine and Pharmacological Characterization at Human Excitatory Amino Acid Transporter Subtypes 1, 2, and 3. Faure, S., Jensen, A.A., Maurat, V., Gu, X., Sagot, E., Aitken, D.J., Bolte, J., Gefflaut, T., Bunch, L. J. Med. Chem. (2006) [Pubmed]
  20. Distribution of glutamate transporters in the human placenta. Noorlander, C.W., de Graan, P.N., Nikkels, P.G., Schrama, L.H., Visser, G.H. Placenta (2004) [Pubmed]
  21. DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters. Shimamoto, K., Lebrun, B., Yasuda-Kamatani, Y., Sakaitani, M., Shigeri, Y., Yumoto, N., Nakajima, T. Mol. Pharmacol. (1998) [Pubmed]
  22. Role of glutamate transporters in the regulation of glutathione levels in human macrophages. Rimaniol, A.C., Mialocq, P., Clayette, P., Dormont, D., Gras, G. Am. J. Physiol., Cell Physiol. (2001) [Pubmed]
  23. Expression of the glial glutamate transporter EAAT2 in the human CNS: an immunohistochemical study. Milton, I.D., Banner, S.J., Ince, P.G., Piggott, N.H., Fray, A.E., Thatcher, N., Horne, C.H., Shaw, P.J. Brain Res. Mol. Brain Res. (1997) [Pubmed]
  24. Positive and negative regulation of EAAT2 by NF-kappaB: a role for N-myc in TNFalpha-controlled repression. Sitcheran, R., Gupta, P., Fisher, P.B., Baldwin, A.S. EMBO J. (2005) [Pubmed]
  25. Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. Arriza, J.L., Fairman, W.A., Wadiche, J.I., Murdoch, G.H., Kavanaugh, M.P., Amara, S.G. J. Neurosci. (1994) [Pubmed]
  26. Benzodiazepines differently modulate EAAT1/GLAST and EAAT2/GLT1 glutamate transporters expressed in CHO cells. Palmada, M., Kinne-Saffran, E., Centelles, J.J., Kinne, R.K. Neurochem. Int. (2002) [Pubmed]
  27. Cysteine-scanning mutagenesis reveals a conformationally sensitive reentrant pore-loop in the glutamate transporter GLT-1. Grunewald, M., Menaker, D., Kanner, B.I. J. Biol. Chem. (2002) [Pubmed]
  28. Post-translational regulation of EAAT2 function by co-expressed ubiquitin ligase Nedd4-2 is impacted by SGK kinases. Boehmer, C., Palmada, M., Rajamanickam, J., Schniepp, R., Amara, S., Lang, F. J. Neurochem. (2006) [Pubmed]
  29. Constitutive ion fluxes and substrate binding domains of human glutamate transporters. Vandenberg, R.J., Arriza, J.L., Amara, S.G., Kavanaugh, M.P. J. Biol. Chem. (1995) [Pubmed]
  30. Regulation of astrocytic glutamate transporter expression by Akt: evidence for a selective transcriptional effect on the GLT-1/EAAT2 subtype. Li, L.B., Toan, S.V., Zelenaia, O., Watson, D.J., Wolfe, J.H., Rothstein, J.D., Robinson, M.B. J. Neurochem. (2006) [Pubmed]
  31. Over-expression of the human EAAT2 glutamate transporter within neurons of mouse organotypic hippocampal slice cultures leads to increased vulnerability of CA1 pyramidal cells. Selkirk, J.V., Stiefel, T.H., Stone, I.M., Naeve, G.S., Foster, A.C., Poulsen, D.J. Eur. J. Neurosci. (2005) [Pubmed]
  32. Distribution of glutamate transporters in the hippocampus of patients with pharmaco-resistant temporal lobe epilepsy. Proper, E.A., Hoogland, G., Kappen, S.M., Jansen, G.H., Rensen, M.G., Schrama, L.H., van Veelen, C.W., van Rijen, P.C., van Nieuwenhuizen, O., Gispen, W.H., de Graan, P.N. Brain (2002) [Pubmed]
  33. 5'-heterogeneity of the human excitatory amino acid transporter cDNA EAAT2 (GLT-1). Münch, C., Schwalenstöcker, B., Knappenberger, B., Liebau, S., Völkel, H., Ludolph, A.C., Meyer, T. Neuroreport (1998) [Pubmed]
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