excitatory amino acid transporter 1

Summary

Summary: A glial type glutamate plasma membrane transporter protein found predominately in ASTROCYTES. It is also expressed in HEART and SKELETAL MUSCLE and in the PLACENTA.

Top Publications

  1. Guo F, Sun F, Yu J, Wang Q, Tu D, Mao X, et al. Abnormal expressions of glutamate transporters and metabotropic glutamate receptor 1 in the spontaneously epileptic rat hippocampus. Brain Res Bull. 2010;81:510-6 pubmed publisher
    ..Our data show that epileptogenesis in SER are associated with regulations of glutamate transporters and mGluR1, which might be potential targets for therapy in genetic epilepsy. ..
  2. Rose E, Koo J, Antflick J, Ahmed S, Angers S, Hampson D. Glutamate transporter coupling to Na,K-ATPase. J Neurosci. 2009;29:8143-55 pubmed publisher
    ..These findings demonstrate that glutamate transporters and Na,K-ATPases are part of the same macromolecular complexes and operate as a functional unit to regulate glutamatergic neurotransmission...
  3. Shin J, Nguyen K, Pow D, Knight T, Buljan V, Bennett M, et al. Distribution of glutamate transporter GLAST in membranes of cultured astrocytes in the presence of glutamate transport substrates and ATP. Neurochem Res. 2009;34:1758-66 pubmed publisher
    ..The present data suggest that GLAST can rapidly and specifically respond to changes in the cellular environment thus potentially helping to fine-tune the functions of astrocytes. ..
  4. Soustelle L, Besson M, Rival T, Birman S. Terminal glial differentiation involves regulated expression of the excitatory amino acid transporters in the Drosophila embryonic CNS. Dev Biol. 2002;248:294-306 pubmed
  5. Bringmann A, Pannicke T, Biedermann B, Francke M, Iandiev I, Grosche J, et al. Role of retinal glial cells in neurotransmitter uptake and metabolism. Neurochem Int. 2009;54:143-60 pubmed publisher
  6. Bjørnsen L, Eid T, Holmseth S, Danbolt N, Spencer D, de Lanerolle N. Changes in glial glutamate transporters in human epileptogenic hippocampus: inadequate explanation for high extracellular glutamate during seizures. Neurobiol Dis. 2007;25:319-30 pubmed
  7. Shigeri Y, Seal R, Shimamoto K. Molecular pharmacology of glutamate transporters, EAATs and VGLUTs. Brain Res Brain Res Rev. 2004;45:250-65 pubmed
    ..This review summarizes the development of these indispensable pharmacological tools, which have been critical to our understanding of normal and abnormal synaptic transmission. ..
  8. Matsugami T, Tanemura K, Mieda M, Nakatomi R, Yamada K, Kondo T, et al. From the Cover: Indispensability of the glutamate transporters GLAST and GLT1 to brain development. Proc Natl Acad Sci U S A. 2006;103:12161-6 pubmed
  9. Liu Y, Yang C, Chen M, Sun S, Tzeng S. Ca(2+)-dependent reduction of glutamate aspartate transporter GLAST expression in astrocytes by P2X(7) receptor-mediated phosphoinositide 3-kinase signaling. J Neurochem. 2010;113:213-27 pubmed publisher

More Information

Publications62

  1. Karlsson R, Tanaka K, Heilig M, Holmes A. Loss of glial glutamate and aspartate transporter (excitatory amino acid transporter 1) causes locomotor hyperactivity and exaggerated responses to psychotomimetics: rescue by haloperidol and metabotropic glutamate 2/3 agonist. Biol Psychiatry. 2008;64:810-4 pubmed publisher
    ..The glial glutamate and aspartate transporter (GLAST) (excitatory amino acid transporter 1 [EAAT1]) regulates extracellular glutamate levels via uptake into glia, but the consequences of ..
  2. Sullivan S, Macnab L, Björkman S, Colditz P, Pow D. GLAST1b, the exon-9 skipping form of the glutamate-aspartate transporter EAAT1 is a sensitive marker of neuronal dysfunction in the hypoxic brain. Neuroscience. 2007;149:434-45 pubmed
    ..We propose that GLAST1b represents a novel and sensitive marker for the detection of neurons at risk of dying in response to hypoxic and other excitotoxic insults and may have wider applicability in experimental and clinical contexts. ..
  3. Takatsuru Y, Iino M, Tanaka K, Ozawa S. Contribution of glutamate transporter GLT-1 to removal of synaptically released glutamate at climbing fiber-Purkinje cell synapses. Neurosci Lett. 2007;420:85-9 pubmed
    ..We conclude that GLT-1 plays a minor role compared to GLAST in clearing synaptically released glutamate at CF-PC synapses. ..
  4. Chandley M, Szebeni K, Szebeni A, Crawford J, Stockmeier C, Turecki G, et al. Gene expression deficits in pontine locus coeruleus astrocytes in men with major depressive disorder. J Psychiatry Neurosci. 2013;38:276-84 pubmed publisher
    ..These findings suggest that increased glutamatergic activity in the LC occurs in men with MDD. ..
  5. Ryan R, Mitrovic A, Vandenberg R. The chloride permeation pathway of a glutamate transporter and its proximity to the glutamate translocation pathway. J Biol Chem. 2004;279:20742-51 pubmed
    ..This study will provide the foundation for beginning to understand how transporters can function as both transporters and ion channels. ..
  6. Bai N, Hayashi H, Aida T, Namekata K, Harada T, Mishina M, et al. Dock3 interaction with a glutamate-receptor NR2D subunit protects neurons from excitotoxicity. Mol Brain. 2013;6:22 pubmed publisher
  7. Ohgoh M, Hanada T, Smith T, Hashimoto T, Ueno M, Yamanishi Y, et al. Altered expression of glutamate transporters in experimental autoimmune encephalomyelitis. J Neuroimmunol. 2002;125:170-8 pubmed
  8. Ryan R, Compton E, Mindell J. Functional characterization of a Na+-dependent aspartate transporter from Pyrococcus horikoshii. J Biol Chem. 2009;284:17540-8 pubmed publisher
    ..We propose a kinetic model of transport in which at least two Na+ ions are coupled to the cotransport of each aspartate molecule by GltPh, and where an ion- and substrate-free transporter reorients to complete the transport cycle...
  9. Walsh T, McClellan J, McCarthy S, Addington A, Pierce S, Cooper G, et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science. 2008;320:539-43 pubmed publisher
    ..These results suggest that multiple, individually rare mutations altering genes in neurodevelopmental pathways contribute to schizophrenia. ..
  10. Rival T, Soustelle L, Strambi C, Besson M, Iché M, Birman S. Decreasing glutamate buffering capacity triggers oxidative stress and neuropil degeneration in the Drosophila brain. Curr Biol. 2004;14:599-605 pubmed
    ..This suggests that the dEAAT1-deficient fly provides a powerful genetic model system for molecular analysis of glutamate-mediated neurodegeneration. ..
  11. Liu L, Su Y, Yang W, Xiao M, Gao J, Hu G. Disruption of neuronal-glial-vascular units in the hippocampus of ovariectomized mice injected with D-galactose. Neuroscience. 2010;169:596-608 pubmed publisher
  12. Gegelashvili M, Rodriguez Kern A, Sung L, Shimamoto K, Gegelashvili G. Glutamate transporter GLAST/EAAT1 directs cell surface expression of FXYD2/gamma subunit of Na, K-ATPase in human fetal astrocytes. Neurochem Int. 2007;50:916-20 pubmed
  13. Deneen B, Ho R, Lukaszewicz A, Hochstim C, Gronostajski R, Anderson D. The transcription factor NFIA controls the onset of gliogenesis in the developing spinal cord. Neuron. 2006;52:953-68 pubmed
    ..At later stages, NFIA promotes migration and differentiation of astrocyte precursors, a function that is antagonized in oligodendrocyte precursors by Olig2. ..
  14. Poulsen C, Schousboe I, Sarup A, White H, Schousboe A. Effect of topiramate and dBcAMP on expression of the glutamate transporters GLAST and GLT-1 in astrocytes cultured separately, or together with neurons. Neurochem Int. 2006;48:657-61 pubmed
    ..025) in the membrane expression of GLAST. In case of GLT-1, culture in the presence of 30 microM topiramate for 1 and 10 days led to alterations in the total, cytoplamic and membrane expression of the oligomeric form of the transporter. ..
  15. Choudary P, Molnar M, Evans S, Tomita H, Li J, Vawter M, et al. Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc Natl Acad Sci U S A. 2005;102:15653-8 pubmed
    ..These findings point to previously undiscovered molecular underpinnings of the pathophysiology of major depression and offer potentially new pharmacological targets for treating depression. ..
  16. Gilley J, Kernie S. Excitatory amino acid transporter 2 and excitatory amino acid transporter 1 negatively regulate calcium-dependent proliferation of hippocampal neural progenitor cells and are persistently upregulated after injury. Eur J Neurosci. 2011;34:1712-23 pubmed publisher
    ..we previously characterized the expression of excitatory amino acid transporter 2 (GltI) and excitatory amino acid transporter 1 (Glast) on early neural progenitors in vivo...
  17. Rao V, Bowen K, Dempsey R. Transient focal cerebral ischemia down-regulates glutamate transporters GLT-1 and EAAC1 expression in rat brain. Neurochem Res. 2001;26:497-502 pubmed
    ..Glutamate transporter down-regulation may disrupt the normal clearance of the synaptically-released glutamate and may contribute to the ischemic neuronal death. ..
  18. Kalariti N, Lembessis P, Koutsilieris M. Characterization of the glutametergic system in MG-63 osteoblast-like osteosarcoma cells. Anticancer Res. 2004;24:3923-9 pubmed
    ..R3, mGluR.4, mGlu.R5 and mGlu.R8 mRNA. However, we did not detect the mRNA expression of NR2C, NR3B, mGlu.R6 and mGlu.R7 mRNA. Our data suggest that MG-63 cells can be used as a model for studying the possible role of Glu beyond CNS. ..
  19. Rauen T, Wiessner M. Fine tuning of glutamate uptake and degradation in glial cells: common transcriptional regulation of GLAST1 and GS. Neurochem Int. 2000;37:179-89 pubmed
  20. Kalariti N, Lembessis P, Papageorgiou E, Pissimissis N, Koutsilieris M. Regulation of the mGluR5, EAAT1 and GS expression by glucocorticoids in MG-63 osteoblast-like osteosarcoma cells. J Musculoskelet Neuronal Interact. 2007;7:113-8 pubmed
    ..Components of the glutamatergic system may play a role in bone pathophysiology. ..
  21. Nguyen K, Shin J, Rae C, Nanitsos E, Acosta G, Pow D, et al. Rottlerin inhibits (Na+, K+)-ATPase activity in brain tissue and alters D-aspartate dependent redistribution of glutamate transporter GLAST in cultured astrocytes. Neurochem Res. 2009;34:1767-74 pubmed publisher
  22. Scott H, Pow D, Tannenberg A, Dodd P. Aberrant expression of the glutamate transporter excitatory amino acid transporter 1 (EAAT1) in Alzheimer's disease. J Neurosci. 2002;22:RC206 pubmed
    ..In this study, we examined the cellular localization of the glial glutamate transporter excitatory amino acid transporter 1 (EAAT1) in the cerebral cortex of control, Alzheimer's disease, and non-Alzheimer dementia cases...
  23. Poitry Yamate C, Vutskits L, Rauen T. Neuronal-induced and glutamate-dependent activation of glial glutamate transporter function. J Neurochem. 2002;82:987-97 pubmed
    ..Together, these results suggest an activity-dependent neuronal feedback system for rapid astroglial glutamate transporter regulation where neuron-derived glutamate is the physiological signal that triggers transporter function. ..
  24. Karlsson R, Tanaka K, Saksida L, Bussey T, Heilig M, Holmes A. Assessment of glutamate transporter GLAST (EAAT1)-deficient mice for phenotypes relevant to the negative and executive/cognitive symptoms of schizophrenia. Neuropsychopharmacology. 2009;34:1578-89 pubmed publisher
    ..These findings demonstrate that gene deletion of GLAST produces select phenotypic abnormalities related to the negative and cognitive symptoms of schizophrenia. ..
  25. Zink M, Vollmayr B, Gebicke Haerter P, Henn F. Reduced expression of glutamate transporters vGluT1, EAAT2 and EAAT4 in learned helpless rats, an animal model of depression. Neuropharmacology. 2010;58:465-73 pubmed publisher
    ..The findings are in concert with antidepressant effects of NMDA-receptor antagonists and the hypotheses that impaired astroglial functions contribute to the pathogenesis of affective disorders. ..
  26. Flatscher Bader T, Wilce P. Impact of alcohol abuse on protein expression of midkine and excitatory amino acid transporter 1 in the human prefrontal cortex. Alcohol Clin Exp Res. 2008;32:1849-58 pubmed publisher
    ..cortex and found that the levels of mRNA encoding the neurotrophic factor, midkine (MDK), and the excitatory amino acid transporter 1 (EAAT1) were significantly higher in alcoholics compared with nonalcoholic controls...
  27. Mitosek Szewczyk K, Sulkowski G, Stelmasiak Z, Struzynska L. Expression of glutamate transporters GLT-1 and GLAST in different regions of rat brain during the course of experimental autoimmune encephalomyelitis. Neuroscience. 2008;155:45-52 pubmed publisher
  28. Aronica E, Gorter J, Ijlst Keizers H, Rozemuller A, Yankaya B, Leenstra S, et al. Expression and functional role of mGluR3 and mGluR5 in human astrocytes and glioma cells: opposite regulation of glutamate transporter proteins. Eur J Neurosci. 2003;17:2106-18 pubmed
  29. Kim S, Choi S, Chao W, Volsky D. 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. J Neurochem. 2003;87:1485-98 pubmed
    b>Excitatory amino acid transporter 1 (EAAT1) is one of the two glial glutamate transporters that clear the extracellular glutamate generated during neuronal signal transmission. Here, we cloned and characterized a 2...
  30. Sullivan S, Lee A, Bjorkman S, Miller S, Sullivan R, Poronnik P, et al. Cytoskeletal anchoring of GLAST determines susceptibility to brain damage: an identified role for GFAP. J Biol Chem. 2007;282:29414-23 pubmed
    ..These data indicate that the cytoskeleton of the astrocyte plays an important role in protecting the brain against glutamate-mediated excitotoxicity. ..
  31. Huang S, Vandenberg R. Mutations in transmembrane domains 5 and 7 of the human excitatory amino acid transporter 1 affect the substrate-activated anion channel. Biochemistry. 2007;46:9685-92 pubmed
  32. Miguel Hidalgo J, Waltzer R, Whittom A, Austin M, Rajkowska G, Stockmeier C. Glial and glutamatergic markers in depression, alcoholism, and their comorbidity. J Affect Disord. 2010;127:230-40 pubmed publisher
    ..There are differential changes in the expression of glial glutamatergic markers in depression and alcoholism, suggesting a depletion of certain aspects of glutamatergic processing in depression. ..
  33. Rival T, Soustelle L, Cattaert D, Strambi C, Iché M, Birman S. Physiological requirement for the glutamate transporter dEAAT1 at the adult Drosophila neuromuscular junction. J Neurobiol. 2006;66:1061-74 pubmed
    ..Therefore, glutamate reuptake by glial cells is required to ensure normal activity of the Drosophila NMJ, but only in adult flies. ..
  34. Vallejo Illarramendi A, Domercq M, Matute C. A novel alternative splicing form of excitatory amino acid transporter 1 is a negative regulator of glutamate uptake. J Neurochem. 2005;95:341-8 pubmed
    ..Together, these results indicate that the EAAT1ex9skip splice variant is a negative regulator of full-length EAAT1 function in the human brain. ..
  35. Cimarosti H, Jones N, O Shea R, Pow D, Salbego C, Beart P. Hypoxic preconditioning in neonatal rat brain involves regulation of excitatory amino acid transporter 2 and estrogen receptor alpha. Neurosci Lett. 2005;385:52-7 pubmed
    ..The endogenous molecular mechanisms modulated by hypoxia preconditioning may contribute to the development of hypoxia-induced ischemic tolerance, and may provide novel therapeutic targets for the treatment of cerebral ischemia. ..
  36. Susarla B, Seal R, Zelenaia O, Watson D, Wolfe J, Amara S, et al. Differential regulation of GLAST immunoreactivity and activity by protein kinase C: evidence for modification of amino and carboxyl termini. J Neurochem. 2004;91:1151-63 pubmed
  37. Skytt D, Madsen K, Pajęcka K, Schousboe A, Waagepetersen H. Characterization of primary and secondary cultures of astrocytes prepared from mouse cerebral cortex. Neurochem Res. 2010;35:2043-52 pubmed publisher
    ..This provides flexibility with regard to preparation and use of these cultures for a variety of purposes. ..
  38. Furuya T, Pan Z, Kashiwagi K. Role of retinal glial cell glutamate transporters in retinal ganglion cell survival following stimulation of NMDA receptor. Curr Eye Res. 2012;37:170-8 pubmed publisher
    ..GLAST and GLT-1 may have different roles in the survival of RGCs mediated by retinal glial cells. These results suggest that the NMDA-associated induction of GLTs plays an important role in RGC survival. ..
  39. Park C, Cha J, Park S, Lee P, Kim J, Kim H, et al. Differential expression of two glutamate transporters, GLAST and GLT-1, in an experimental rat model of glaucoma. Exp Brain Res. 2009;197:101-9 pubmed publisher
    ..These results suggest that GLT-1 may be a prerequisite for the maintenance of glutamate homeostasis in the retina undergoing glaucoma. ..
  40. Weng H, Aravindan N, Cata J, Chen J, Shaw A, Dougherty P. Spinal glial glutamate transporters downregulate in rats with taxol-induced hyperalgesia. Neurosci Lett. 2005;386:18-22 pubmed
    ..These data indicate that downregulation of glutamate transporters may contribute to the development of hyperalgesia induced by taxol and suggest that glutamate transporters may be a new target for treatment of pain. ..
  41. Ji Q, Li Z, Tang Y, Mo Y, Yao H, Saiyin C. [Effect of electroacupuncture intervention on behavioral changes and hippocampal excitatory amino acid transporter mRNA expression in depression rats]. Zhen Ci Yan Jiu. 2013;38:202-7, 219 pubmed
  42. Bigini P, Bastone A, Mennini T. Glutamate transporters in the spinal cord of the wobbler mouse. Neuroreport. 2001;12:1815-20 pubmed
    ..Plasma concentrations of excitatory amino acids were no different at any time examined. Our results exclude the involvement of decrease in glutamate GLT 1 transporter in the motor neuron degeneration in wobbler mice...
  43. Zhou M, Xu G, Xie M, Zhang X, Schools G, Ma L, et al. TWIK-1 and TREK-1 are potassium channels contributing significantly to astrocyte passive conductance in rat hippocampal slices. J Neurosci. 2009;29:8551-64 pubmed publisher
    ..These results support TWIK-1 and TREK-1 as being the major components of the long-sought K(+) channels underlying the passive conductance of mature hippocampal astrocytes. ..
  44. Erikson K, Dorman D, Lash L, Aschner M. Manganese inhalation by rhesus monkeys is associated with brain regional changes in biomarkers of neurotoxicity. Toxicol Sci. 2007;97:459-66 pubmed
    ..g., GSH was increased in the frontal cortex and decreased in the caudate despite two- to threefold increases in Mn concentrations in these regions). ..
  45. Delyfer M, Forster V, Neveux N, Picaud S, Leveillard T, Sahel J. Evidence for glutamate-mediated excitotoxic mechanisms during photoreceptor degeneration in the rd1 mouse retina. Mol Vis. 2005;11:688-96 pubmed
    ..This may indicate that excessive glutamate levels further contribute to rod cell degeneration, thus implying the occurrence of non-cell autonomous mechanisms in the degenerative process in the rd1 retina. ..
  46. Castaldo P, Magi S, Cataldi M, Arcangeli S, Lariccia V, Nasti A, et al. Altered regulation of glutamate release and decreased functional activity and expression of GLT1 and GLAST glutamate transporters in the hippocampus of adolescent rats perinatally exposed to Delta(9)-THC. Pharmacol Res. 2010;61:334-41 pubmed publisher
    ..Collectively, these data demonstrate that perinatal exposure to cannabinoids induces long-term impairment in hippocampal glutamatergic neurotransmission that persist into adolescence. ..
  47. Yang Y, Wang X, Frerking M, Zhou Q. Delivery of AMPA receptors to perisynaptic sites precedes the full expression of long-term potentiation. Proc Natl Acad Sci U S A. 2008;105:11388-93 pubmed publisher
    ..These results demonstrate that AMPARs are rapidly trafficked to perisynaptic sites shortly after LTP induction and suggest that the delivery and maintenance of perisynaptic AMPARs may serve as a checkpoint in the expression of LTP. ..
  48. Aprico K, Beart P, Crawford D, O Shea R. Comparison of [(3)H]-(2S,4R)-4-methylglutamate and [(3)H]D-aspartate as ligands for binding and autoradiographic analyses of glutamate transporters. Neurochem Int. 2007;51:507-16 pubmed
    ..Overall, in tissue sections [(3)H]4MG proved unsuitable for studying the autoradiographic localization of EAATs apparently due to its inability to selectively discriminate Na(+)-dependent binding to Glu transporters. ..
  49. Muller D, Kuiper H, Boneker C, Mömke S, Drogemuller C, Chowdhary B, et al. Assignment of BGLAP, BMP2, CHST4, SLC1A3, SLC4A1, SLC9A5 and SLC20A1 to equine chromosomes by FISH and confirmation by RH mapping. Anim Genet. 2005;36:457-61 pubmed
  50. Vallejo Illarramendi A, Torres Ramos M, Melone M, Conti F, Matute C. Clozapine reduces GLT-1 expression and glutamate uptake in astrocyte cultures. Glia. 2005;50:276-9 pubmed
    ..A better understanding of the molecular events by which antipsychotics regulate Glu uptake can contribute to identify new targets for the treatment of schizophrenia. ..
  51. Mäenpää H, Gegelashvili G, Tähti H. Expression of glutamate transporter subtypes in cultured retinal pigment epithelial and retinoblastoma cells. Curr Eye Res. 2004;28:159-65 pubmed
    ..Unaltered steady-state expression of this carrier and chloride-channel protein hints at posttranslational mechanisms of regulation of EAAT4. ..
  52. King N, Lin H, McGivan J, Suleiman M. Aspartate transporter expression and activity in hypertrophic rat heart and ischaemia-reperfusion injury. J Physiol. 2004;556:849-58 pubmed
    ..These results suggest that increased aspartate transporter expression and activity in hypertrophy helps facilitate aspartate entry into hypertrophied cardiomyocytes, which in turn leads to improved myocardial protection. ..
  53. Li X, Newbern J, Wu Y, Morgan Smith M, Zhong J, Charron J, et al. MEK Is a Key Regulator of Gliogenesis in the Developing Brain. Neuron. 2012;75:1035-50 pubmed publisher
    ..We conclude that MEK is essential for acquisition of gliogenic competence by radial progenitors and that levels of MEK activity regulate gliogenesis in the developing cortex. ..