amino acid transport system x ag


Summary: A family of POTASSIUM and SODIUM-dependent acidic amino acid transporters that demonstrate a high affinity for GLUTAMIC ACID and ASPARTIC ACID. Several variants of this system are found in neuronal tissue.

Top Publications

  1. Xin W, Weng H, Dougherty P. Plasticity in expression of the glutamate transporters GLT-1 and GLAST in spinal dorsal horn glial cells following partial sciatic nerve ligation. Mol Pain. 2009;5:15 pubmed publisher
    ..Neurons showed no expression of GLT-1 or GLAST at any time point. These results indicate that the expression of glutamate transporters in astrocytes and microglia are differentially regulated following nerve injury. ..
  2. Binns B, Huang Y, Goettl V, Hackshaw K, Stephens R. Glutamate uptake is attenuated in spinal deep dorsal and ventral horn in the rat spinal nerve ligation model. Brain Res. 2005;1041:38-47 pubmed
    ..The study suggests that plasticity related to spinal nerve injury produces widespread alteration in glutamate transporter function that may contribute to the pathophysiology of neuropathic pain. ..
  3. Tzingounis A, Wadiche J. Glutamate transporters: confining runaway excitation by shaping synaptic transmission. Nat Rev Neurosci. 2007;8:935-47 pubmed
    ..We highlight how the diversity of glutamate-transporter function relates to transporter location, density and affinity. ..
  4. Beurrier C, Bonvento G, Kerkerian Le Goff L, Gubellini P. Role of glutamate transporters in corticostriatal synaptic transmission. Neuroscience. 2009;158:1608-15 pubmed publisher
    ..Moreover, the control of glutamate concentration in the synaptic cleft by GTs may play a role in a number of degenerative disorders characterized by the hyperactivity of corticostriatal pathway, as well as in synaptic plasticity. ..
  5. Melzer N, Biela A, Fahlke C. Glutamate modifies ion conduction and voltage-dependent gating of excitatory amino acid transporter-associated anion channels. J Biol Chem. 2003;278:50112-9 pubmed
    ..These results are incompatible with the notion that glutamate only increases the open probability of the anion pore associated with glutamate transporters and demonstrate unique gating mechanisms of EAAT-associated anion channels. ..
  6. Campbell S, Hablitz J. Glutamate transporters regulate excitability in local networks in rat neocortex. Neuroscience. 2004;127:625-35 pubmed
    ..Our results indicate that uptake inhibition produces an elevation of extracellular glutamate levels and activation of N-methyl-D-aspartate receptors. ..
  7. Tao F, Liaw W, Zhang B, Yaster M, Rothstein J, Johns R, et al. Evidence of neuronal excitatory amino acid carrier 1 expression in rat dorsal root ganglion neurons and their central terminals. Neuroscience. 2004;123:1045-51 pubmed
    ..Our findings suggest that EAAC1 might play an important role in transmission and modulation of nociceptive information via the regulation of pre-synaptically released glutamate. ..
  8. 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. ..
  9. Tian G, Lai L, Guo H, Lin Y, Butchbach M, Chang Y, et al. Translational control of glial glutamate transporter EAAT2 expression. J Biol Chem. 2007;282:1727-37 pubmed

More Information


  1. Grewer C, Rauen T. Electrogenic glutamate transporters in the CNS: molecular mechanism, pre-steady-state kinetics, and their impact on synaptic signaling. J Membr Biol. 2005;203:1-20 pubmed
    ..Finally, we discuss how synaptic glutamate transporters impact on glutamate receptor activity and how transporters may shape excitatory synaptic transmission. ..
  2. Koch H, Larsson H. Small-scale molecular motions accomplish glutamate uptake in human glutamate transporters. J Neurosci. 2005;25:1730-6 pubmed
    ..Furthermore, we show that, despite the multimeric nature of glutamate transporters, the subunits function independently. ..
  3. Huang Y, Dykes Hoberg M, Tanaka K, Rothstein J, Bergles D. Climbing fiber activation of EAAT4 transporters and kainate receptors in cerebellar Purkinje cells. J Neurosci. 2004;24:103-11 pubmed
    ..In GluR5 knock-out mice, this current was dramatically reduced, indicating that CF excitation of PCs involves two distinct classes of ionotropic glutamate receptors, AMPA receptors and GluR5-containing kainate receptors. ..
  4. Zhang G, Raol Y, Hsu F, Brooks Kayal A. Long-term alterations in glutamate receptor and transporter expression following early-life seizures are associated with increased seizure susceptibility. J Neurochem. 2004;88:91-101 pubmed
    ..The current data suggest that early-life status-epilepticus can result in permanent alterations in glutamate receptor and transporter gene expression, which may contribute to a lower seizure threshold. ..
  5. Butchbach M, Tian G, Guo H, Lin C. Association of excitatory amino acid transporters, especially EAAT2, with cholesterol-rich lipid raft microdomains: importance for excitatory amino acid transporter localization and function. J Biol Chem. 2004;279:34388-96 pubmed
  6. Huang Y, Sinha S, Tanaka K, Rothstein J, Bergles D. Astrocyte glutamate transporters regulate metabotropic glutamate receptor-mediated excitation of hippocampal interneurons. J Neurosci. 2004;24:4551-9 pubmed
  7. Stoffel W, Körner R, Wachtmann D, Keller B. Functional analysis of glutamate transporters in excitatory synaptic transmission of GLAST1 and GLAST1/EAAC1 deficient mice. Brain Res Mol Brain Res. 2004;128:170-81 pubmed
  8. Angulo M, Kozlov A, Charpak S, Audinat E. Glutamate released from glial cells synchronizes neuronal activity in the hippocampus. J Neurosci. 2004;24:6920-7 pubmed
    ..In conclusion, our results show that the glial glutamate release occurs spontaneously and synchronizes the neuronal activity in the hippocampus. ..
  9. Colin A, Faideau M, Dufour N, Auregan G, Hassig R, Andrieu T, et al. Engineered lentiviral vector targeting astrocytes in vivo. Glia. 2009;57:667-79 pubmed publisher
    ..These vectors provide new opportunities for cell type-specific gene transfer in the CNS. ..
  10. Yernool D, Boudker O, Jin Y, Gouaux E. Structure of a glutamate transporter homologue from Pyrococcus horikoshii. Nature. 2004;431:811-8 pubmed
    ..We propose that transport of glutamate is achieved by movements of the hairpins that allow alternating access to either side of the membrane...
  11. Guillet B, Velly L, Canolle B, Masmejean F, Nieoullon A, Pisano P. Differential regulation by protein kinases of activity and cell surface expression of glutamate transporters in neuron-enriched cultures. Neurochem Int. 2005;46:337-46 pubmed
    ..These processes may represent rapid adaptive responses to changes in the cellular environment, which significantly contribute to regulation of EAA transmission and further prevent possible excitotoxic events. ..
  12. Weng H, Chen J, Cata J. Inhibition of glutamate uptake in the spinal cord induces hyperalgesia and increased responses of spinal dorsal horn neurons to peripheral afferent stimulation. Neuroscience. 2006;138:1351-60 pubmed
  13. Tao Z, Zhang Z, Grewer C. Neutralization of the aspartic acid residue Asp-367, but not Asp-454, inhibits binding of Na+ to the glutamate-free form and cycling of the glutamate transporter EAAC1. J Biol Chem. 2006;281:10263-72 pubmed
    ..Our data are consistent with a model in which Asp-367, but not Asp-454, is involved in coordinating the bound Na(+) in the glutamate-free transporter form. ..
  14. Custer S, Garden G, Gill N, Rueb U, Libby R, Schultz C, et al. Bergmann glia expression of polyglutamine-expanded ataxin-7 produces neurodegeneration by impairing glutamate transport. Nat Neurosci. 2006;9:1302-11 pubmed
    ..Our studies indicate that impairment of glutamate transport secondary to glial dysfunction contributes to SCA7 neurodegeneration, and suggest a similar role for glial dysfunction in other polyglutamine diseases and SCAs. ..
  15. Tao Y, Gu J, Stephens R. Role of spinal cord glutamate transporter during normal sensory transmission and pathological pain states. Mol Pain. 2005;1:30 pubmed
  16. Veruki M, Mørkve S, Hartveit E. Activation of a presynaptic glutamate transporter regulates synaptic transmission through electrical signaling. Nat Neurosci. 2006;9:1388-96 pubmed
    ..Given the evidence for presynaptic glutamate transporters, similar mechanisms could be of general importance for transmission in the nervous system. ..
  17. Koch H, Hubbard J, Larsson H. Voltage-independent sodium-binding events reported by the 4B-4C loop in the human glutamate transporter excitatory amino acid transporter 3. J Biol Chem. 2007;282:24547-53 pubmed
  18. Voutsinos Porche B, Knott G, Tanaka K, Quairiaux C, Welker E, Bonvento G. Glial glutamate transporters and maturation of the mouse somatosensory cortex. Cereb Cortex. 2003;13:1110-21 pubmed
    ..Our data suggest that astrocyte-neuron interactions via the glial glutamate transporters are involved in the functional maturation of the whisker representation in the somatosensory cortex. ..
  19. Sung B, Lim G, Mao J. Altered expression and uptake activity of spinal glutamate transporters after nerve injury contribute to the pathogenesis of neuropathic pain in rats. J Neurosci. 2003;23:2899-910 pubmed
  20. Matthias K, Kirchhoff F, Seifert G, Hüttmann K, Matyash M, Kettenmann H, et al. Segregated expression of AMPA-type glutamate receptors and glutamate transporters defines distinct astrocyte populations in the mouse hippocampus. J Neurosci. 2003;23:1750-8 pubmed
    ..The observed heterogeneity of cells with GFAP promoter-regulated EGFP expression and S100beta/GFAP immunoreactivity challenges the hitherto accepted definition of astrocytes. ..
  21. Dunlop J, Beal McIlvain H, She Y, Howland D. Impaired spinal cord glutamate transport capacity and reduced sensitivity to riluzole in a transgenic superoxide dismutase mutant rat model of amyotrophic lateral sclerosis. J Neurosci. 2003;23:1688-96 pubmed
  22. Smith R, Haroutunian V, Davis K, Meador Woodruff J. Expression of excitatory amino acid transporter transcripts in the thalamus of subjects with schizophrenia. Am J Psychiatry. 2001;158:1393-9 pubmed
  23. Ueda Y, Doi T, Tsuru N, Tokumaru J, Mitsuyama Y. Expression of glutamate transporters and ionotropic glutamate receptors in GLAST knockout mice. Brain Res Mol Brain Res. 2002;104:120-6 pubmed
  24. Mao J, Sung B, Ji R, Lim G. Chronic morphine induces downregulation of spinal glutamate transporters: implications in morphine tolerance and abnormal pain sensitivity. J Neurosci. 2002;22:8312-23 pubmed
    ..These results indicate that spinal GTs may contribute to the neural mechanisms of morphine tolerance and associated abnormal pain sensitivity by means of regulating regional glutamate homeostasis. ..
  25. Mao J, Sung B, Ji R, Lim G. Neuronal apoptosis associated with morphine tolerance: evidence for an opioid-induced neurotoxic mechanism. J Neurosci. 2002;22:7650-61 pubmed
    ..These results indicate an opioid-induced neurotoxic consequence regulated by the NMDAR-caspase pathway, a mechanism that may have clinical implications in opioid therapy and substance abuse. ..
  26. Levenson J, Weeber E, Selcher J, Kategaya L, Sweatt J, Eskin A. Long-term potentiation and contextual fear conditioning increase neuronal glutamate uptake. Nat Neurosci. 2002;5:155-61 pubmed
    ..These results indicate that regulation of glutamate uptake may be important for maintaining the level of synaptic strength during long-term changes in synaptic efficacy. ..
  27. Brasnjo G, Otis T. Neuronal glutamate transporters control activation of postsynaptic metabotropic glutamate receptors and influence cerebellar long-term depression. Neuron. 2001;31:607-16 pubmed
    ..Postsynaptic glutamate uptake may serve as a general mechanism for regulating mGluR-initiated synaptic depression. ..
  28. Diamond J. Neuronal glutamate transporters limit activation of NMDA receptors by neurotransmitter spillover on CA1 pyramidal cells. J Neurosci. 2001;21:8328-38 pubmed
    ..Because glutamate transporters operate most effectively at negative membrane potentials, these results suggest that activation of NMDA receptors by spillover may depend on postsynaptic activity. ..
  29. Ingram E, Wiseman J, Tessler S, Emson P. Reduction of glial glutamate transporters in the parietal cortex and hippocampus of the EL mouse. J Neurochem. 2001;79:564-75 pubmed
    ..The glial glutamate transporter down-regulation reported here may play a role in seizure initiation, spread and maintenance in the EL mouse. ..
  30. Gorter J, van Vliet E, Proper E, de Graan P, Ghijsen W, Lopes da Silva F, et al. Glutamate transporters alterations in the reorganizing dentate gyrus are associated with progressive seizure activity in chronic epileptic rats. J Comp Neurol. 2002;442:365-77 pubmed
  31. Cholet N, Pellerin L, Magistretti P, Hamel E. Similar perisynaptic glial localization for the Na+,K+-ATPase alpha 2 subunit and the glutamate transporters GLAST and GLT-1 in the rat somatosensory cortex. Cereb Cortex. 2002;12:515-25 pubmed
    ..Altogether these results demonstrate that alpha(2), GLAST and GLT-1 have comparable perisynaptic distribution within cortical astrocytes most likely associated with glutamatergic synapses. ..
  32. Voutsinos Porche B, Bonvento G, Tanaka K, Steiner P, Welker E, Chatton J, et al. Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex. Neuron. 2003;37:275-86 pubmed
    ..These data suggest that a metabolic crosstalk takes place between neurons and astrocytes in the developing cortex, which would be regulated by synaptic activity and mediated by glial glutamate transporters. ..
  33. 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
  34. Rojas H, Colina C, Ramos M, Benaim G, Jaffe E, Caputo C, et al. Na+ entry via glutamate transporter activates the reverse Na+/Ca2+ exchange and triggers Ca(i)2+-induced Ca2+ release in rat cerebellar Type-1 astrocytes. J Neurochem. 2007;100:1188-202 pubmed
  35. Zheng K, Scimemi A, Rusakov D. Receptor actions of synaptically released glutamate: the role of transporters on the scale from nanometers to microns. Biophys J. 2008;95:4584-96 pubmed publisher
    ..The results provide a quantitative framework for a better understanding of the relationship between glutamate transporters and glutamate receptor signaling. ..
  36. Noyan Ashraf M, Brandizzi F, Juurlink B. Constitutive nuclear localization of activated caspase 3 in subpopulations of the astroglial family of cells. Glia. 2005;49:588-93 pubmed
    ..We conclude that Bergmann glia and a subpopulation of astrocytes throughout the CNS express activated caspase 3 in nuclei to fulfill a yet-to-be defined non-apoptotic function. GLIA. ..
  37. Eulenburg V, Gomeza J. Neurotransmitter transporters expressed in glial cells as regulators of synapse function. Brain Res Rev. 2010;63:103-12 pubmed publisher
    ..The analysis of these mechanisms will enhance not only our understanding of synapse function but will reveal new therapeutic strategies for the treatment of human neurological diseases. ..
  38. 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. ..
  39. Zuo Z, Fang H. Glutamate transporter type 3 attenuates the activation of N-methyl-D-aspartate receptors co-expressed in Xenopus oocytes. J Exp Biol. 2005;208:2063-70 pubmed
    ..These results suggest that EAAT3 regulates the amplitude of NMDAR currents at pre-saturated concentrations of glutamate to EAAT3. Thus, EAATs, by rapidly regulating glutamate concentrations near NMDAR, modulate NMDAR current/activation. ..
  40. Noorlander C, de Graan P, Nikkels P, Schrama L, Visser G. Distribution of glutamate transporters in the human placenta. Placenta. 2004;25:489-95 pubmed
    ..No differences were found in the distribution of the glutamate transporters between control and IUGR placentae. Our data show specific localization of EAAT1, EAAT2 and EAAT3 in the human placenta during development. ..
  41. Hisano S. Vesicular glutamate transporters in the brain. Anat Sci Int. 2003;78:191-204 pubmed
  42. Re D, Nafia I, Melon C, Shimamoto K, Kerkerian Le Goff L, Had Aissouni L. Glutamate leakage from a compartmentalized intracellular metabolic pool and activation of the lipoxygenase pathway mediate oxidative astrocyte death by reversed glutamate transport. Glia. 2006;54:47-57 pubmed
    ..In addition, we provide evidence for a minor contribution of the cystine-glutamate antiporter x(c) (-) but a major role of the 5-lipoxygenase pathway in this death mechanism. ..
  43. Byun K, Kim J, Cho S, Hutchinson B, Yang S, Kang K, et al. Alteration of the glutamate and GABA transporters in the hippocampus of the Niemann-Pick disease, type C mouse using proteomic analysis. Proteomics. 2006;6:1230-6 pubmed
    ..In conclusion, our data may provide insight into the understanding of the basic mechanism through perturbation of protein networks and neurotransporter systems in a single gene knockout model of NPC disease. ..
  44. Hamann M, Rossi D, Mohr C, Andrade A, Attwell D. The electrical response of cerebellar Purkinje neurons to simulated ischaemia. Brain. 2005;128:2408-20 pubmed
    ..The glutamate activating these receptors is released both by exocytosis (at early times) and by reversal of a glutamate transporter, apparently in neurons. ..
  45. Olsen D, Dunlap K, Jacob M. Kainate receptors and RNA editing in cholinergic neurons. J Neurochem. 2007;101:327-41 pubmed
    ..Our data suggest that glutamatergic signaling may function as a local circuit mechanism to modulate excitability and calcium signaling during synapse formation and maturation in the CG in vivo. ..
  46. Furuta A, Takashima S, Yokoo H, Rothstein J, Wada K, Iwaki T. Expression of glutamate transporter subtypes during normal human corticogenesis and type II lissencephaly. Brain Res Dev Brain Res. 2005;155:155-64 pubmed
    ..Altered glutamate transporter expression in type II lissencephaly suggests that glutamate metabolism is involved in the formation of the normal cortex and contributes to the disorganized cortex seen in migration disorders. ..
  47. Schicho R, Donnerer J, Liebmann I, Lippe I. Nociceptive transmitter release in the dorsal spinal cord by capsaicin-sensitive fibers after noxious gastric stimulation. Brain Res. 2005;1039:108-15 pubmed
  48. Bauer D, Gupta D, Harotunian V, Meador Woodruff J, McCullumsmith R. Abnormal expression of glutamate transporter and transporter interacting molecules in prefrontal cortex in elderly patients with schizophrenia. Schizophr Res. 2008;104:108-20 pubmed publisher
    ..These data indicate that proteins involved in glutamate reuptake and cycling are altered in the cortex in schizophrenia, and may provide potential targets for future treatment strategies. ..
  49. Wang S, Lin T, Lu C, Huang W. Osthole and imperatorin, the active constituents of Cnidium monnieri (L.) Cusson, facilitate glutamate release from rat hippocampal nerve terminals. Neurochem Int. 2008;53:416-23 pubmed publisher
    ..Together, these results suggest that osthole or imperatorin effects a facilitation of glutamate release from nerve terminals by positively modulating N-and P/Q-type Ca(2+) channel activation through a signaling cascade involving PKC. ..
  50. Schniepp R, Kohler K, Ladewig T, Guenther E, Henke G, Palmada M, et al. Retinal colocalization and in vitro interaction of the glutamate transporter EAAT3 and the serum- and glucocorticoid-inducible kinase SGK1 [correction]. Invest Ophthalmol Vis Sci. 2004;45:1442-9 pubmed
    ..This function is shared by protein kinase B (PKB). The experiments reveal a novel mechanism regulating EAAT3, which may be essential for the function of the retinal ganglion cells. ..
  51. Shimamoto K, Sakai R, Takaoka K, Yumoto N, Nakajima T, Amara S, et al. Characterization of novel L-threo-beta-benzyloxyaspartate derivatives, potent blockers of the glutamate transporters. Mol Pharmacol. 2004;65:1008-15 pubmed
    ..Taken together, these findings indicate that novel TBOA analogs, especially TFB-TBOA, should serve as useful tools for elucidating the physiological roles of the glutamate transporters. ..
  52. Lin S, Tsai R, Shen C, Lin F, Wang J, Hsin S, et al. Co-administration of ultra-low dose naloxone attenuates morphine tolerance in rats via attenuation of NMDA receptor neurotransmission and suppression of neuroinflammation in the spinal cords. Pharmacol Biochem Behav. 2010;96:236-45 pubmed publisher
    ..These findings demonstrated that attenuation of glutamatergic transmission and neuroinflammation by ultra-low dose naloxone co-infusion preserves the lasting antinociceptive effect of morphine in rats chronically infused with morphine. ..
  53. Gu Q, Zhao J, Fei J, Schwarz W. Modulation of Na(+),K(+) pumping and neurotransmitter uptake by beta-amyloid. Neuroscience. 2004;126:61-7 pubmed
    ..The domain between amino acids 12 and 28 of Abeta seems to play a crucial role for inhibition of EAAC1. The inhibition of EAAC1 by neurotoxic, elevated extracellular glutamate levels may contribute to Alzheimer's pathogenesis. ..