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Gene Review

Slc1a3  -  solute carrier family 1 (glial high...

Rattus norvegicus

Synonyms: EAAT1, 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

  • Excitatory synaptic events activate rapid electrogenic glial glutamate transporter currents similar to those elicited by exogenous glutamate in other preparations [9].
  • Three glutamate transporters have been identified in rat, including astroglial transporters GLAST and GLT-1 and a neuronal transporter EAAC1 [10].
  • Astroglial membrane GLAST densities ranked as follows: Bergmann > cerebellar granular layer approximately hippocampus > cerebellar white matter [11].
  • GLAST is found in both neurons and astroglia [12].
  • Analysis of such synaptic EAAT currents suggests that, on average, postsynaptic EAATs take up approximately 1,300,000 glutamate molecules in response to a single climbing fiber action potential [13].

Chemical compound and disease context of Slc1a3


Biological context of Slc1a3

  • The amino acid sequence of GLAST suggests a distinctive structure and membrane topology, with some conserved motifs also present in prokaryotic glutamate transporters [17].
  • A GLAST-specific cDNA clone was isolated from a rat brain cDNA library [17].
  • Here we demonstrate that the complete open reading frame of GLAST-1 mRNA and corresponding 69 kDa protein are expressed in rat bone in vivo [18].
  • Mouse excitatory amino acid transporter EAAT2: isolation, characterization, and proximity to neuroexcitability loci on mouse chromosome 2 [19].
  • Therefore the 70-kDa isoform differs only in the degree of glycosylation from the 64-kDa GLAST-1 isoform [20].

Anatomical context of Slc1a3

  • These data suggest that GLAST may be involved in the regulation of neurotransmitter concentration in central nervous system [17].
  • In situ hybridization reveals a strikingly high density of GLAST mRNA in the Purkinje cell layer of cerebellum, presumably in the Bergmann glia cells, and a less dense distribution throughout the cerebrum [17].
  • However, when neurons are seeded and co-cultured on a layer of hippocampal astrocytes, they do not develop any immunoreactivity towards GLAST or GLT antibodies [21].
  • In apparent contrast, all factors completely failed to affect GLT-1 and GLAST expression in astroglial cultures from the cerebellum, mesencephalon, and spinal cord between 36 h and 7 days [22].
  • This has led us to propose that GLAST-1a has an opposite orientation in the cell membrane to GLAST-1 [18].

Associations of Slc1a3 with chemical compounds


Regulatory relationships of Slc1a3


Other interactions of Slc1a3

  • In blocking experiments using neutralizing antibodies and by incubation of astrocytes with recombinant cytokines, tumor necrosis factor-alpha (TNF-alpha) was identified as being responsible for the down-modulation of GLAST [28].
  • Intriguingly, alterations of caveolin gene expression in response to cAMP or TGF-alpha coincided with reciprocal and brain-region specific changes in glial glutamate transporter GLT-1 expression [29].
  • Thus, long-term treatment with the group I mGluR agonist, DHPG, causes down-regulation of GLAST, whereas the group II agonist, DCG-IV, has an opposite effect on the expression of GLAST in astrocytes [30].
  • In contrast, hypoxic preconditioning had no effect on the levels of EAAT1 and ERbeta in any of the brain regions studied at any of the time points analyzed [31].

Analytical, diagnostic and therapeutic context of Slc1a3


  1. Correlation between myocardial malate/aspartate shuttle activity and EAAT1 protein expression in hyper- and hypothyroidism. Ralphe, J.C., Bedell, K., Segar, J.L., Scholz, T.D. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  2. Selective induction of glial glutamate transporter GLT-1 by hypertonic stress in C6 glioma cells. Imura, T., Shimohama, S., Kageyama, T., Kimura, J. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  3. Altered expression of the glutamate transporter EAAC1 in neurons and immature oligodendrocytes after transient forebrain ischemia. Gottlieb, M., Domercq, M., Matute, C. J. Cereb. Blood Flow Metab. (2000) [Pubmed]
  4. Early loss of the glutamate transporter splice-variant GLT-1v in rat cerebral cortex following lateral fluid-percussion injury. Yi, J.H., Pow, D.V., Hazell, A.S. Glia (2005) [Pubmed]
  5. The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2-nonenal in the Alzheimer's disease brain: the role of Abeta1-42. Lauderback, C.M., Hackett, J.M., Huang, F.F., Keller, J.N., Szweda, L.I., Markesbery, W.R., Butterfield, D.A. J. Neurochem. (2001) [Pubmed]
  6. Selective down-regulation of the astrocyte glutamate transporters GLT-1 and GLAST within the medial thalamus in experimental Wernicke's encephalopathy. Hazell, A.S., Rao, K.V., Danbolt, N.C., Pow, D.V., Butterworth, R.F. J. Neurochem. (2001) [Pubmed]
  7. Changes in the expression of glial glutamate transporters in the rat brain accompanied with morphine dependence and naloxone-precipitated withdrawal. Ozawa, T., Nakagawa, T., Shige, K., Minami, M., Satoh, M. Brain Res. (2001) [Pubmed]
  8. Beta-amyloid enhances glial glutamate uptake activity and attenuates synaptic efficacy. Ikegaya, Y., Matsuura, S., Ueno, S., Baba, A., Yamada, M.K., Nishiyama, N., Matsuki, N. J. Biol. Chem. (2002) [Pubmed]
  9. Glial contributions to excitatory neurotransmission in cultured hippocampal cells. Mennerick, S., Zorumski, C.F. Nature (1994) [Pubmed]
  10. Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Rothstein, J.D., Dykes-Hoberg, M., Pardo, C.A., Bristol, L.A., Jin, L., Kuncl, R.W., Kanai, Y., Hediger, M.A., Wang, Y., Schielke, J.P., Welty, D.F. Neuron (1996) [Pubmed]
  11. Glutamate transporters in glial plasma membranes: highly differentiated localizations revealed by quantitative ultrastructural immunocytochemistry. Chaudhry, F.A., Lehre, K.P., van Lookeren Campagne, M., Ottersen, O.P., Danbolt, N.C., Storm-Mathisen, J. Neuron (1995) [Pubmed]
  12. Localization of neuronal and glial glutamate transporters. Rothstein, J.D., Martin, L., Levey, A.I., Dykes-Hoberg, M., Jin, L., Wu, D., Nash, N., Kuncl, R.W. Neuron (1994) [Pubmed]
  13. Isolation of glutamate transport-coupled charge flux and estimation of glutamate uptake at the climbing fiber-Purkinje cell synapse. Brasnjo, G., Otis, T.S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  14. Gene transfer of GLT-1, a glutamate transporter, into the nucleus accumbens shell attenuates methamphetamine- and morphine-induced conditioned place preference in rats. Fujio, M., Nakagawa, T., Sekiya, Y., Ozawa, T., Suzuki, Y., Minami, M., Satoh, M., Kaneko, S. Eur. J. Neurosci. (2005) [Pubmed]
  15. Decreased cortical levels of astrocytic glutamate transport protein GLT-1 in a rat model of posttraumatic epilepsy. Samuelsson, C., Kumlien, E., Flink, R., Lindholm, D., Ronne-Engström, E. Neurosci. Lett. (2000) [Pubmed]
  16. Glutamate stimulates neurotrophin expression in cultured Müller cells. Taylor, S., Srinivasan, B., Wordinger, R.J., Roque, R.S. Brain Res. Mol. Brain Res. (2003) [Pubmed]
  17. Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain. Storck, T., Schulte, S., Hofmann, K., Stoffel, W. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  18. The open reading frame of the Na(+)-dependent glutamate transporter GLAST-1 is expressed in bone and a splice variant of this molecule is expressed in bone and brain. Huggett, J., Vaughan-Thomas, A., Mason, D. FEBS Lett. (2000) [Pubmed]
  19. Mouse excitatory amino acid transporter EAAT2: isolation, characterization, and proximity to neuroexcitability loci on mouse chromosome 2. Kirschner, M.A., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Amara, S.G. Genomics (1994) [Pubmed]
  20. UDP galactose:ceramide galactosyltransferase and glutamate/aspartate transporter. Copurification, separation and characterization of the two glycoproteins. Schulte, S., Stoffel, W. Eur. J. Biochem. (1995) [Pubmed]
  21. Astrocytes repress the neuronal expression of GLAST and GLT glutamate transporters in cultured hippocampal neurons from embryonic rats. Plachez, C., Martin, A., Guiramand, J., Récasens, M. Neurochem. Int. (2004) [Pubmed]
  22. CNS region-specific regulation of glial glutamate transporter expression. Schlüter, K., Figiel, M., Rozyczka, J., Engele, J. Eur. J. Neurosci. (2002) [Pubmed]
  23. Localization and function of the brain excitatory amino acid transporter type 1 in cardiac mitochondria. Ralphe, J.C., Segar, J.L., Schutte, B.C., Scholz, T.D. J. Mol. Cell. Cardiol. (2004) [Pubmed]
  24. Expression of high-affinity neuronal and glial glutamate transporters in the rat optic nerve. Choi, I., Chiu, S.Y. Glia (1997) [Pubmed]
  25. Endothelin-1 decreases glutamate uptake in primary cultured rat astrocytes. Leonova, J., Thorlin, T., Aberg, N.D., Eriksson, P.S., Rönnbäck, L., Hansson, E. Am. J. Physiol., Cell Physiol. (2001) [Pubmed]
  26. The GLT-1 and GLAST glutamate transporters are expressed on morphologically distinct astrocytes and regulated by neuronal activity in primary hippocampal cocultures. Perego, C., Vanoni, C., Bossi, M., Massari, S., Basudev, H., Longhi, R., Pietrini, G. J. Neurochem. (2000) [Pubmed]
  27. The extracellular signal-regulated kinase cascade suppresses amyloid beta protein-induced promotion of glutamate clearance in cultured rat cortical astrocytes. Abe, K., Misawa, M. Brain Res. (2003) [Pubmed]
  28. Autoantigen specific T cells inhibit glutamate uptake in astrocytes by decreasing expression of astrocytic glutamate transporter GLAST: a mechanism mediated by tumor necrosis factor-alpha. Korn, T., Magnus, T., Jung, S. FASEB J. (2005) [Pubmed]
  29. Caveolin and GLT-1 gene expression is reciprocally regulated in primary astrocytes: association of GLT-1 with non-caveolar lipid rafts. Zschocke, J., Bayatti, N., Behl, C. Glia (2005) [Pubmed]
  30. The high-affinity glutamate transporters GLT1, GLAST, and EAAT4 are regulated via different signalling mechanisms. Gegelashvili, G., Dehnes, Y., Danbolt, N.C., Schousboe, A. Neurochem. Int. (2000) [Pubmed]
  31. Hypoxic preconditioning in neonatal rat brain involves regulation of excitatory amino acid transporter 2 and estrogen receptor alpha. Cimarosti, H., Jones, N.M., O'Shea, R.D., Pow, D.V., Salbego, C., Beart, P.M. Neurosci. Lett. (2005) [Pubmed]
  32. Identification of a glutamate/aspartate transporter in the rat cochlea. Li, H.S., Niedzielski, A.S., Beisel, K.W., Hiel, H., Wenthold, R.J., Morley, B.J. Hear. Res. (1994) [Pubmed]
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