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Gene Review

Slc1a2  -  solute carrier family 1 (glial high...

Rattus norvegicus

Synonyms: Eaat2, Excitatory amino acid transporter 2, GLT-1, GLUT-R, Glt, ...
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Disease relevance of Slc1a2

  • The glutamate transporter GLT-1 from Rattus norvegicus was expressed at high level in BHK cells using the Semliki Forest virus expression system [1].
  • Further real-time quantitative RT-PCR assays showed that global ischemia resulted in a decrease in GLT-1 mRNA level of hippocampal CA1 region [2].
  • These results suggested that astrocytic GLT-1 participated in the clearance of extracellular Glu and protected neurons from NMDA receptor-mediated toxicity [3].
  • Bilateral infusion of the recombinant adenoviruses into the NAc shell efficiently increased GLT-1 expression surrounding the infusion site, at least during the period 2-8 days after the infusion [4].
  • Consistent with these data, C6 glioma expressed EAAC1- but not GLT1- and GLAST-like immunoreactivity [5].

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

  • Chronic restraint stress up-regulates GLT-1 mRNA and protein expression in the rat hippocampus: reversal by tianeptine [21].
  • The synthetic glucocorticoid dexamethasone provoked a marked increase of GLT-1 transcription and protein levels in cortical astrocytes, whereas GLAST expression remained unaffected [17].
  • Moreover, we monitored brain region-specific differences, since all corticosteroids used in this study failed to alter the expression of GLT-1 in midbrain and cerebellar glia, although expression levels of both corticosteroid receptor subtypes were similar in all brain regions analyzed [17].
  • Glycosylated and non-glycosylated GLT-1 were transported to the plasma membrane with equal efficiency [1].
  • For GLT-1 expressed in COS cells, coexpression of Ajuba did not affect the transporter's K(m) or V(max) for glutamate [22].

Associations of Slc1a2 with chemical compounds

  • Accordingly, the current study examined the distribution and regulation of the glia glutamate transporter GLT-1 and the recently identified GLT isoform, GLT-1b, in the hippocampus of rats subjected to chronic restraint stress (CRS) [21].
  • Dexamethasone, however, modestly enhanced GLT-1 expression in cerebellar glia in combination with the DNA methyltransferase inhibitor 5-aza-2-deoxycytidine, suggesting that suppression of GLT-1 expression in cerebellar cultures may at least in part be epigenetically mediated by a DNA methylation-dependent process [17].
  • Histidine 326 is critical for the function of GLT-1, a (Na+ + K+)-coupled glutamate transporter from rat brain [23].
  • The promoting effect of dexamethasone on GLT-1 gene expression and function was abolished by the GR antagonist mifepristone [17].
  • A predominant role of the GR was further supported by the observation that corticosterone could elevate GLT-1 expression in a dose-dependent manner, whereas aldosterone, the physiological ligand of the mineralocorticoid receptor, exerted only weak effects even when applied at high concentrations [17].

Regulatory relationships of Slc1a2

  • RNase protection assays showed that of the two glial transporters, mRNA for GLAST was expressed at much higher level than was GLT-1 [24].
  • We suggest that one or both of the GLT-1 RNA species induced by Wnt-1 either fail to be translated or yield abnormal translation products that are quickly degraded [25].

Other interactions of Slc1a2

  • In conclusion, this study highlights the occurrence of the reciprocal regulation of caveolin and GLT-1 expression during processes such as astrocyte differentiation via common signaling pathways [26].
  • 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 [27].
  • Lipopolysaccharide increases microglial GLT-1 expression and glutamate uptake capacity in vitro by a mechanism dependent on TNF-alpha [28].
  • These findings indicate that the induction of GLT-1 mRNA by HS is independent of the MAPK pathways [29].
  • However, the possible functional role of EAAC1 in preventing neuron death has not been resolved as compared with glial glutamate transporters such as GLT-1 [30].

Analytical, diagnostic and therapeutic context of Slc1a2


  1. High-yield expression, reconstitution and structure of the recombinant, fully functional glutamate transporter GLT-1 from Rattus norvegicus. Raunser, S., Haase, W., Bostina, M., Parcej, D.N., Kühlbrandt, W. J. Mol. Biol. (2005) [Pubmed]
  2. Glutamate transporter function of rat hippocampal astrocytes is impaired following the global ischemia. Yeh, T.H., Hwang, H.M., Chen, J.J., Wu, T., Li, A.H., Wang, H.L. Neurobiol. Dis. (2005) [Pubmed]
  3. Selective blockade of astrocytic glutamate transporter GLT-1 with dihydrokainate prevents neuronal death during ouabain treatment of astrocyte/neuron cocultures. Kawahara, K., Hosoya, R., Sato, H., Tanaka, M., Nakajima, T., Iwabuchi, S. Glia (2002) [Pubmed]
  4. 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]
  5. Comparison of Na+-dependent glutamate transport activity in synaptosomes, C6 glioma, and Xenopus oocytes expressing excitatory amino acid carrier 1 (EAAC1). Dowd, L.A., Coyle, A.J., Rothstein, J.D., Pritchett, D.B., Robinson, M.B. Mol. Pharmacol. (1996) [Pubmed]
  6. Effect of gene transfer of GLT-1, a glutamate transporter, into the locus coeruleus by recombinant adenoviruses on morphine physical dependence in rats. Ozawa, T., Nakagawa, T., Sekiya, Y., Minami, M., Satoh, M. Eur. J. Neurosci. (2004) [Pubmed]
  7. 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]
  8. 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]
  9. Biotinylation of single cysteine mutants of the glutamate transporter GLT-1 from rat brain reveals its unusual topology. Grunewald, M., Bendahan, A., Kanner, B.I. Neuron (1998) [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. The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: relation to energy metabolism and glutamatergic neurotransmission. Norenberg, M.D., Huo, Z., Neary, J.T., Roig-Cantesano, A. Glia (1997) [Pubmed]
  14. The effects of PBN (phenyl-butyl-nitrone) on GLT-1 levels and on the extracellular levels of amino acids and energy metabolites in a model of iron-induced posttraumatic epilepsy. Samuelsson, C., Kumlien, E., Elfving, A., Lindholm, D., Ronne-Engström, E. Epilepsy Res. (2003) [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. Volume-regulated anion channels are the predominant contributors to release of excitatory amino acids in the ischemic cortical penumbra. Feustel, P.J., Jin, Y., Kimelberg, H.K. Stroke (2004) [Pubmed]
  17. Differential promotion of glutamate transporter expression and function by glucocorticoids in astrocytes from various brain regions. Zschocke, J., Bayatti, N., Clement, A.M., Witan, H., Figiel, M., Engele, J., Behl, C. J. Biol. Chem. (2005) [Pubmed]
  18. Modulation of spinal nociceptive processing through the glutamate transporter GLT-1. Niederberger, E., Schmidtko, A., Rothstein, J.D., Geisslinger, G., Tegeder, I. Neuroscience (2003) [Pubmed]
  19. A splice variant of glutamate transporter GLT1/EAAT2 expressed in neurons: cloning and localization in rat nervous system. Schmitt, A., Asan, E., Lesch, K.P., Kugler, P. Neuroscience (2002) [Pubmed]
  20. Functional significance of the preconditioning-induced down-regulation of glutamate transporter GLT-1 in neuron/astrocyte co-cultures. Kosugi, T., Kawahara, K., Yamada, T., Nakajima, T., Tanaka, M. Neurochem. Res. (2005) [Pubmed]
  21. Chronic restraint stress up-regulates GLT-1 mRNA and protein expression in the rat hippocampus: reversal by tianeptine. Reagan, L.P., Rosell, D.R., Wood, G.E., Spedding, M., Muñoz, C., Rothstein, J., McEwen, B.S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  22. The amino terminus of the glial glutamate transporter GLT-1 interacts with the LIM protein Ajuba. Marie, H., Billups, D., Bedford, F.K., Dumoulin, A., Goyal, R.K., Longmore, G.D., Moss, S.J., Attwell, D. Mol. Cell. Neurosci. (2002) [Pubmed]
  23. Histidine 326 is critical for the function of GLT-1, a (Na+ + K+)-coupled glutamate transporter from rat brain. Zhang, Y., Pines, G., Kanner, B.I. J. Biol. Chem. (1994) [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. Wnt signaling induces GLT-1 expression in rat C6 glioma cells. Palos, T.P., Zheng, S., Howard, B.D. J. Neurochem. (1999) [Pubmed]
  26. 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]
  27. CNS region-specific regulation of glial glutamate transporter expression. Schlüter, K., Figiel, M., Rozyczka, J., Engele, J. Eur. J. Neurosci. (2002) [Pubmed]
  28. Lipopolysaccharide increases microglial GLT-1 expression and glutamate uptake capacity in vitro by a mechanism dependent on TNF-alpha. Persson, M., Brantefjord, M., Hansson, E., Rönnbäck, L. Glia (2005) [Pubmed]
  29. 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]
  30. Unique anti-apoptotic activity of EAAC1 in injured motor neurons. Kiryu-Seo, S., Gamo, K., Tachibana, T., Tanaka, K., Kiyama, H. EMBO J. (2006) [Pubmed]
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