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Gene Review

SLC1A3  -  solute carrier family 1 (glial high...

Homo sapiens

Synonyms: EA6, EAAT1, Excitatory amino acid transporter 1, GLAST, GLAST-1, ...
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Disease relevance of SLC1A3


Psychiatry related information on SLC1A3


High impact information on SLC1A3


Chemical compound and disease context of SLC1A3

  • In retinal amacrine and ganglion cells, EAAT5 is colocalized with the serum and glucocorticoid inducible kinase SGK1, a serine/threonine kinase known to regulate transport [13].
  • L-glutamate per se was gliotoxic only at concentrations much higher than the maximum reached with the potent EAAT substrate inhibitor L-trans-pyrrolidine-2,4-dicarboxylate (PDC), and toxicity was lower [14].

Biological context of SLC1A3


Anatomical context of SLC1A3

  • EAAC1 is selective for neurons, while GLT-1 and GLAST are selective for astroglia [2].
  • The kinetic parameters and pharmacological characteristics of transport mediated by each EAAT subtype were determined in transfected mammalian cells by radio-label uptake and in microinjected oocytes by voltage-clamp measurements [16].
  • By contrast, there was only a modest loss (20% decrease from control) of immunoreactive protein EAAC1 in ALS motor cortex, and there was no appreciable change in GLAST [2].
  • In this study, the distribution of protein and mRNA of EAAT subtypes was examined in the hippocampus of TLE patients with hippocampal sclerosis (HS group) and without hippocampal sclerosis (non-HS group), and in autopsy controls without neurological disorders [18].
  • Expression of excitatory amino acid transporter transcripts in the thalamus of subjects with schizophrenia [19].

Associations of SLC1A3 with chemical compounds


Regulatory relationships of SLC1A3


Other interactions of SLC1A3

  • Glutamate induces a current in Xenopus oocytes expressing EAAT1, but not in water-injected oocytes, which is decreased by co-expression of Nedd4-2, an effect reversed by additional co-expression of S422DSGK1, SGK3 and T308D,S473DPKB, but not K127NSGK1 [24].
  • In order to investigate this hypothesis further, the expression of several 'glutamatergic' markers, the metabotropic glutamate receptors (mGluRs; mGluR3, 5) and the human excitatory amino acid transporter (EAAT2) were compared in the PFC of normal individuals and schizophrenics [25].
  • Here, we cloned and characterized a 2.1-kb promoter region of human EAAT1 and investigated its function in the transcriptional regulation of the EAAT1 gene in human primary astrocytes [26].
  • In a case with "burnt out" HIVE following highly active antiretroviral therapy (HAART), EAAT-1 expression was mild, identical to that of HLA-DR and CD68 in the white matter and cortex and involved perineuronal microglial cells [27].
  • Occasional EAAT-1 expressing AMM were found in patients with short survival, whereas diffuse EAAT-1 expression by AMM was observed in cases with long survival (24 to 33 months) that most often were heterozygous for Met/Val at codon 129 of the PRNP gene [28].

Analytical, diagnostic and therapeutic context of SLC1A3


  1. Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures. Jen, J.C., Wan, J., Palos, T.P., Howard, B.D., Baloh, R.W. Neurology (2005) [Pubmed]
  2. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Rothstein, J.D., Van Kammen, M., Levey, A.I., Martin, L.J., Kuncl, R.W. Ann. Neurol. (1995) [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. A family based study implicates solute carrier family 1-member 3 (SLC1A3) gene in attention-deficit/hyperactivity disorder. Turic, D., Langley, K., Williams, H., Norton, N., Williams, N.M., Moskvina, V., Van den Bree, M.B., Owen, M.J., Thapar, A., O'Donovan, M.C. Biol. Psychiatry (2005) [Pubmed]
  5. Glutamate transporters in platelets: EAAT1 decrease in aging and in Alzheimer's disease. Zoia, C., Cogliati, T., Tagliabue, E., Cavaletti, G., Sala, G., Galimberti, G., Rivolta, I., Rossi, V., Frattola, L., Ferrarese, C. Neurobiol. Aging (2004) [Pubmed]
  6. Striatal excitatory amino acid transporter transcript expression in schizophrenia, bipolar disorder, and major depressive disorder. McCullumsmith, R.E., Meador-Woodruff, J.H. Neuropsychopharmacology (2002) [Pubmed]
  7. Involvement of glial glutamate transporters in morphine dependence. Nakagawa, T., Satoh, M. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  8. Fibroblast glutamate transport in aging and in AD: correlations with disease severity. Zoia, C.P., Tagliabue, E., Isella, V., Begni, B., Fumagalli, L., Brighina, L., Appollonio, I., Racchi, M., Ferrarese, C. Neurobiol. Aging (2005) [Pubmed]
  9. An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Fairman, W.A., Vandenberg, R.J., Arriza, J.L., Kavanaugh, M.P., Amara, S.G. Nature (1995) [Pubmed]
  10. 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]
  11. The Transcription Factor NFIA Controls the Onset of Gliogenesis in the Developing Spinal Cord. Deneen, B., Ho, R., Lukaszewicz, A., Hochstim, C.J., Gronostajski, R.M., Anderson, D.J. Neuron (2006) [Pubmed]
  12. A model for the topology of excitatory amino acid transporters determined by the extracellular accessibility of substituted cysteines. Seal, R.P., Leighton, B.H., Amara, S.G. Neuron (2000) [Pubmed]
  13. Regulation of the excitatory amino acid transporter EAAT5 by the serum and glucocorticoid dependent kinases SGK1 and SGK3. Boehmer, C., Rajamanickam, J., Schniepp, R., Kohler, K., Wulff, P., Kuhl, D., Palmada, M., Lang, F. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  14. Glutamate leakage from a compartmentalized intracellular metabolic pool and activation of the lipoxygenase pathway mediate oxidative astrocyte death by reversed glutamate transport. Re, D.B., Nafia, I., Melon, C., Shimamoto, K., Goff, L.K., Had-Aissouni, L. Glia (2006) [Pubmed]
  15. Localization of the gene (SLC1A3) encoding human glutamate transporter (GluT-1) to 5p13 by fluorescence in situ hybridization. Takai, S., Yamada, K., Kawakami, H., Tanaka, K., Nakamura, S. Cytogenet. Cell Genet. (1995) [Pubmed]
  16. 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]
  17. 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]
  18. 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]
  19. Expression of excitatory amino acid transporter transcripts in the thalamus of subjects with schizophrenia. Smith, R.E., Haroutunian, V., Davis, K.L., Meador-Woodruff, J.H. The American journal of psychiatry. (2001) [Pubmed]
  20. Interaction of L-cysteine with a human excitatory amino acid transporter. Zerangue, N., Kavanaugh, M.P. J. Physiol. (Lond.) (1996) [Pubmed]
  21. The neuronal excitatory amino acid transporter EAAC1/EAAT3: does it represent a major actor at the brain excitatory synapse? Nieoullon, A., Canolle, B., Masmejean, F., Guillet, B., Pisano, P., Lortet, S. J. Neurochem. (2006) [Pubmed]
  22. 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]
  23. High-affinity glutamate transporter GLAST/EAAT1 regulates cell surface expression of glutamine/neutral amino acid transporter ASCT2 in human fetal astrocytes. Gegelashvili, M., Rodriguez-Kern, A., Pirozhkova, I., Zhang, J., Sung, L., Gegelashvili, G. Neurochem. Int. (2006) [Pubmed]
  24. Regulation of the glutamate transporter EAAT1 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid-inducible kinase isoforms SGK1/3 and protein kinase B. Boehmer, C., Henke, G., Schniepp, R., Palmada, M., Rothstein, J.D., Bröer, S., Lang, F. J. Neurochem. (2003) [Pubmed]
  25. Expression of the human excitatory amino acid transporter 2 and metabotropic glutamate receptors 3 and 5 in the prefrontal cortex from normal individuals and patients with schizophrenia. Ohnuma, T., Augood, S.J., Arai, H., McKenna, P.J., Emson, P.C. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  26. Transcriptional regulation of human excitatory amino acid transporter 1 (EAAT1): cloning of the EAAT1 promoter and characterization of its basal and inducible activity in human astrocytes. Kim, S.Y., Choi, S.Y., Chao, W., Volsky, D.J. J. Neurochem. (2003) [Pubmed]
  27. Expression of excitatory amino acid transporter-1 in brain macrophages and microglia of HIV-infected patients. A neuroprotective role for activated microglia? Vallat-Decouvelaere, A.V., Chrétien, F., Gras, G., Le Pavec, G., Dormont, D., Gray, F. J. Neuropathol. Exp. Neurol. (2003) [Pubmed]
  28. Expression of excitatory amino acid transporter-1 (EAAT-1) in brain macrophages and microglia of patients with prion diseases. Chrétien, F., Le Pavec, G., Vallat-Decouvelaere, A.V., Delisle, M.B., Uro-Coste, E., Ironside, J.W., Gambetti, P., Parchi, P., Créminon, C., Dormont, D., Mikol, J., Gray, F., Gras, G. J. Neuropathol. Exp. Neurol. (2004) [Pubmed]
  29. 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]
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