excitatory amino acid transporter 2

Summary

Summary: A glutamate plasma membrane transporter protein found in ASTROCYTES and in the LIVER.

Top Publications

  1. 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. ..
  2. 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
  3. Thone Reineke C, Neumann C, Namsolleck P, Schmerbach K, Krikov M, Schefe J, et al. The beta-lactam antibiotic, ceftriaxone, dramatically improves survival, increases glutamate uptake and induces neurotrophins in stroke. J Hypertens. 2008;26:2426-35 pubmed publisher
    ..Improved neurological performance and survival may be due to neuroprotection by activation of GLT1 and a stimulation of neurotrophins resulting in an increased number of surviving neurons in the penumbra. ..
  4. 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
  5. Ghosh M, Yang Y, Rothstein J, Robinson M. Nuclear factor-?B contributes to neuron-dependent induction of glutamate transporter-1 expression in astrocytes. J Neurosci. 2011;31:9159-69 pubmed publisher
    The glutamate transporter-1 [GLT-1 (excitatory amino acid transporter 2)] subtype of glutamate transporter ensures crisp excitatory signaling and limits excitotoxicity in the CNS...
  6. Bellesi M, Conti F. The mGluR2/3 agonist LY379268 blocks the effects of GLT-1 upregulation on prepulse inhibition of the startle reflex in adult rats. Neuropsychopharmacology. 2010;35:1253-60 pubmed publisher
    ..These results indicate a novel mechanism by which GLT-1 upregulation modulates PPI of the startle. ..
  7. Colton C, Kong Q, Lai L, Zhu M, Seyb K, Cuny G, et al. Identification of translational activators of glial glutamate transporter EAAT2 through cell-based high-throughput screening: an approach to prevent excitotoxicity. J Biomol Screen. 2010;15:653-62 pubmed publisher
    ..These hits provide excellent starting points for developing therapeutic agents to prevent excitotoxicity. ..
  8. Ramos K, Lewis M, Morgan K, Crysdale N, Kroll J, Taylor F, et al. Spinal upregulation of glutamate transporter GLT-1 by ceftriaxone: therapeutic efficacy in a range of experimental nervous system disorders. Neuroscience. 2010;169:1888-900 pubmed publisher
    ..GLT-1 therefore may be a therapeutic target that could improve available treatment options for patients with chronic pain. ..
  9. Bette S, Unger T, Lakowa N, Friedrich M, Engele J. Sequences of the non-coding RNA, NTAB, are contained within the 3'-UTR of human and rat EAAT2/GLT-1 transcripts and act as transcriptional enhancers. Cell Mol Neurobiol. 2011;31:393-9 pubmed publisher
    ..Finally, we unravel that partial Ntab sequences are selectively present in the vicinity of the EAAT2/GLT-1 gene in several other mammalians, implying a conserved function of this sequence in the vertebrate CNS. ..

More Information

Publications62

  1. 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. ..
  2. Bellesi M, Melone M, Gubbini A, Battistacci S, Conti F. GLT-1 upregulation impairs prepulse inhibition of the startle reflex in adult rats. Glia. 2009;57:703-13 pubmed publisher
    ..Our data indicate that GLT-1 regulates PPI of the startle reflex. ..
  3. Lu Z, Zhang W, Zhang N, Jiang J, Luo Q, Qiu Y. The expression of glutamate transporters in chest compression-induced audiogenic epilepsy: a comparative study. Neurol Res. 2008;30:915-9 pubmed publisher
    ..Altering the expression of GLT-1 and EAAC1 through some means might lead them to be potential targets for therapy in cerebral ischemia-related epilepsy. ..
  4. Hammer J, Alvestad S, Osen K, Skare Ø, Sonnewald U, Ottersen O. Expression of glutamine synthetase and glutamate dehydrogenase in the latent phase and chronic phase in the kainate model of temporal lobe epilepsy. Glia. 2008;56:856-68 pubmed publisher
    ..In a situation where glutamate catabolism is in high demand the secondary reduction in GS level may be sufficient to contribute to the seizure proneness that develops between the latent and chronic phases. ..
  5. Lee S, Su Z, Emdad L, Gupta P, Sarkar D, Borjabad A, et al. Mechanism of ceftriaxone induction of excitatory amino acid transporter-2 expression and glutamate uptake in primary human astrocytes. J Biol Chem. 2008;283:13116-23 pubmed publisher
    ..These findings suggest a mechanism for ceftriaxone modulation of glutamate transport and for its potential effects on ameliorating specific neurodegenerative diseases through modulation of extracellular glutamate. ..
  6. Lauriat T, McInnes L. EAAT2 regulation and splicing: relevance to psychiatric and neurological disorders. Mol Psychiatry. 2007;12:1065-78 pubmed
    The excitatory amino acid transporter 2 (EAAT2) is responsible for the majority of glutamate uptake in the brain and its dysregulation has been associated with multiple psychiatric and neurological disorders...
  7. 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
  8. Ouyang Y, Voloboueva L, Xu L, Giffard R. Selective dysfunction of hippocampal CA1 astrocytes contributes to delayed neuronal damage after transient forebrain ischemia. J Neurosci. 2007;27:4253-60 pubmed
    ..We suggest that greater oxidative stress and loss of GLT-1 function selectively in CA1 astrocytes is central to the well known delayed death of CA1 neurons. ..
  9. 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
  10. Carbone M, Duty S, Rattray M. Riluzole elevates GLT-1 activity and levels in striatal astrocytes. Neurochem Int. 2012;60:31-8 pubmed publisher
    ..This observation extends the known pharmacological actions of riluzole, and suggests that this compound may exert its neuroprotective effects through an astrocyte-dependent mechanism. ..
  11. Liu C, Jiao H, Guo Z, Peng Y, Wang W. Up-regulated GLT-1 resists glutamate toxicity and attenuates glutamate-induced calcium loading in cultured neurocytes. Basic Clin Pharmacol Toxicol. 2013;112:19-24 pubmed publisher
    ..In conclusion, GLT-1 up-regulation induced by ceftriaxone plays a positive glutamate transporting role against glutamate toxicity in primary cultured rat cortical cells. ..
  12. Benediktsson A, Marrs G, Tu J, Worley P, Rothstein J, Bergles D, et al. Neuronal activity regulates glutamate transporter dynamics in developing astrocytes. Glia. 2012;60:175-88 pubmed publisher
    ..we examined the subcellular distribution and dynamic remodeling of the predominant GluT GLT-1 (excitatory amino acid transporter 2, EAAT2) in developing hippocampal astrocytes...
  13. Sari Y, Smith K, Ali P, Rebec G. Upregulation of GLT1 attenuates cue-induced reinstatement of cocaine-seeking behavior in rats. J Neurosci. 2009;29:9239-43 pubmed publisher
    ..Our results suggest that glutamate plays a key role in cue-induced relapse to cocaine-seeking behavior, implicating GLT1 as a potential therapeutic target for cocaine addiction...
  14. 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
    ..are labeled with enhanced green fluorescent protein, 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...
  15. Kawakami Z, Kanno H, Ueki T, Terawaki K, Tabuchi M, Ikarashi Y, et al. Neuroprotective effects of yokukansan, a traditional Japanese medicine, on glutamate-mediated excitotoxicity in cultured cells. Neuroscience. 2009;159:1397-407 pubmed publisher
    ..These results suggest that TJ-54 may exert a neuroprotective effect against glutamate-induced excitotoxicity not only by amelioration of dysfunction of astrocytes but also by direct protection of neuronal cells. ..
  16. Holmseth S, Scott H, Real K, Lehre K, Leergaard T, Bjaalie J, et al. The concentrations and distributions of three C-terminal variants of the GLT1 (EAAT2; slc1a2) glutamate transporter protein in rat brain tissue suggest differential regulation. Neuroscience. 2009;162:1055-71 pubmed publisher
  17. 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. ..
  18. Melone M, Bellesi M, Conti F. Synaptic localization of GLT-1a in the rat somatic sensory cortex. Glia. 2009;57:108-17 pubmed publisher
  19. Lee A, Anderson A, Stevens M, Pow D. Exon 4-skipping GLT-1: a new form of an abundantly expressed glutamate transporter. Neurosci Lett. 2011;504:228-31 pubmed publisher
    ..We conclude that exon-4 skipping GLT 1 is abundantly expressed in the brain and may represent either a functional glutamate transporter or a modulator of glutamate transporter function. ..
  20. Kim K, Lee S, Kegelman T, Su Z, Das S, Dash R, et al. Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics. J Cell Physiol. 2011;226:2484-93 pubmed publisher
  21. Tawfik V, Regan M, Haenggeli C, Lacroix Fralish M, Nutile McMenemy N, Perez N, et al. Propentofylline-induced astrocyte modulation leads to alterations in glial glutamate promoter activation following spinal nerve transection. Neuroscience. 2008;152:1086-92 pubmed publisher
    ..The ability of propentofylline to alter glial glutamate transporters highlights the importance of controlling aberrant glial activation in neuropathic pain and suggests one possible mechanism for the anti-allodynic action of this drug. ..
  22. Kanner B. Structure and function of sodium-coupled GABA and glutamate transporters. J Membr Biol. 2006;213:89-100 pubmed
    ..In this review the functional results on prototypes of the two families, the GABA transporter GAT-1 and the glutamate transporters GLT-1 and EAAC1, are described and discussed within the perspective provided by the novel structures. ..
  23. Furness D, Dehnes Y, Akhtar A, Rossi D, Hamann M, Grutle N, et al. A quantitative assessment of glutamate uptake into hippocampal synaptic terminals and astrocytes: new insights into a neuronal role for excitatory amino acid transporter 2 (EAAT2). Neuroscience. 2008;157:80-94 pubmed publisher
    The relative distribution of the excitatory amino acid transporter 2 (EAAT2) between synaptic terminals and astroglia, and the importance of EAAT2 for the uptake into terminals is still unresolved...
  24. 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. ..
  25. Lai P, Huang Y, Wu C, Lai C, Wang P, Chiu T. Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats. J Biomed Sci. 2011;18:69 pubmed publisher
    ..GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury. ..
  26. 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. ..
  27. Dallas M, Boycott H, Atkinson L, Miller A, Boyle J, Pearson H, et al. Hypoxia suppresses glutamate transport in astrocytes. J Neurosci. 2007;27:3946-55 pubmed
    ..Suppression of glutamate uptake via this mechanism may be an important contributory factor in hypoxic/ischemic triggered glutamate excitotoxicity. ..
  28. Vanhoutte N, Abarca Quinones J, Jordan B, Gallez B, Maloteaux J, Hermans E. Enhanced expression of the high affinity glutamate transporter GLT-1 in C6 glioma cells delays tumour progression in rat. Exp Neurol. 2009;218:56-63 pubmed publisher
  29. Massie A, Goursaud S, Schallier A, Vermoesen K, Meshul C, Hermans E, et al. Time-dependent changes in GLT-1 functioning in striatum of hemi-Parkinson rats. Neurochem Int. 2010;57:572-8 pubmed publisher
  30. Chu K, Lee S, Sinn D, Ko S, Kim E, Kim J, et al. Pharmacological Induction of Ischemic Tolerance by Glutamate Transporter-1 (EAAT2) Upregulation. Stroke. 2007;38:177-82 pubmed
    ..05). This study presents evidence that CTX induces ischemic tolerance in focal cerebral ischemia and that this is mediated by GLT-1 upregulation. ..
  31. Raudensky J, Yamamoto B. Effects of chronic unpredictable stress and methamphetamine on hippocampal glutamate function. Brain Res. 2007;1135:129-35 pubmed
  32. Qu S, Kanner B. Substrates and non-transportable analogues induce structural rearrangements at the extracellular entrance of the glial glutamate transporter GLT-1/EAAT2. J Biol Chem. 2008;283:26391-400 pubmed publisher
    ..Our results are consistent with the proposal that HP2 serves as the extracellular gate of the transporter and indicate that glutamate and the two analogues induce distinct conformations of HP2. ..
  33. Ratelade J, Bennett J, Verkman A. Evidence against cellular internalization in vivo of NMO-IgG, aquaporin-4, and excitatory amino acid transporter 2 in neuromyelitis optica. J Biol Chem. 2011;286:45156-64 pubmed publisher
    ..We conclude that astrocyte endocytosis of NMO-IgG, AQP4, and EAAT2 is not a significant consequence of AQP4 autoantibody in vivo, challenging generally accepted views about NMO pathogenesis. ..
  34. Maeda S, Kawamoto A, Yatani Y, Shirakawa H, Nakagawa T, Kaneko S. Gene transfer of GLT-1, a glial glutamate transporter, into the spinal cord by recombinant adenovirus attenuates inflammatory and neuropathic pain in rats. Mol Pain. 2008;4:65 pubmed publisher
    ..Upregulation or functional enhancement of spinal GLT-1 could be a novel strategy for the prevention of pathological pain. ..
  35. Persson M, Rönnbäck L. Microglial self-defence mediated through GLT-1 and glutathione. Amino Acids. 2012;42:207-19 pubmed publisher
    ..This can lead to a defence against oxidative stress and have an antiviral function. ..
  36. Sullivan R, WoldeMussie E, Macnab L, Ruiz G, Pow D. Evoked expression of the glutamate transporter GLT-1c in retinal ganglion cells in human glaucoma and in a rat model. Invest Ophthalmol Vis Sci. 2006;47:3853-9 pubmed
    ..GLT-1c may be a useful indicator of the extent of stress of the retinal ganglion cells and thus a tool for examining outcomes of potential therapeutic and experimental interventions. ..
  37. Deng Y, Xu Z, Xu B, Tian Y, Xin X, Deng X, et al. The protective effect of riluzole on manganese caused disruption of glutamate-glutamine cycle in rats. Brain Res. 2009;1289:106-17 pubmed publisher
    ..These results suggested that Glu-Gln cycle was disrupted by Mn exposure dose dependently; riluzole might antagonize Mn neurotoxicity. ..
  38. Yang Y, Gozen O, Watkins A, Lorenzini I, Lepore A, Gao Y, et al. Presynaptic regulation of astroglial excitatory neurotransmitter transporter GLT1. Neuron. 2009;61:880-94 pubmed publisher
    ..Presynaptic elements dynamically coordinate normal astroglial function and also provide a fundamental signaling mechanism by which altered neuronal function and injury leads to dysregulated astroglia in CNS disease. ..
  39. Desilva T, Kinney H, Borenstein N, Trachtenberg F, Irwin N, Volpe J, et al. The glutamate transporter EAAT2 is transiently expressed in developing human cerebral white matter. J Comp Neurol. 2007;501:879-90 pubmed
  40. Yi J, Hazell A. Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury. Neurochem Int. 2006;48:394-403 pubmed
    ..Such new insight should improve the likelihood of development of novel avenues for therapeutic intervention following TBI. ..
  41. Desilva T, Billiards S, Borenstein N, Trachtenberg F, Volpe J, Kinney H, et al. Glutamate transporter EAAT2 expression is up-regulated in reactive astrocytes in human periventricular leukomalacia. J Comp Neurol. 2008;508:238-48 pubmed publisher
    ..The previously unrecognized up-regulation of EAAT2 in reactive astrocytes and its presence in macrophages in PVL reported here may reflect a response to either hypoxic-ischemic injury or inflammation. ..
  42. Wu X, Kihara T, Akaike A, Niidome T, Sugimoto H. PI3K/Akt/mTOR signaling regulates glutamate transporter 1 in astrocytes. Biochem Biophys Res Commun. 2010;393:514-8 pubmed publisher
    ..In contrast, rapamycin did not affect Akt (Ser473) phosphorylation. Our results suggest that mTOR is a downstream target of the PI3K/Akt pathway regulating GLT1 expression. ..
  43. Escartin C, Brouillet E, Gubellini P, Trioulier Y, Jacquard C, Smadja C, et al. Ciliary neurotrophic factor activates astrocytes, redistributes their glutamate transporters GLAST and GLT-1 to raft microdomains, and improves glutamate handling in vivo. J Neurosci. 2006;26:5978-89 pubmed
    ..Activated astrocytes may therefore be important prosurvival agents in pathological conditions involving defects in glutamate homeostasis. ..
  44. Sheldon A, Robinson M. The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention. Neurochem Int. 2007;51:333-55 pubmed
  45. Miller B, Dorner J, Shou M, Sari Y, Barton S, Sengelaub D, et al. Up-regulation of GLT1 expression increases glutamate uptake and attenuates the Huntington's disease phenotype in the R6/2 mouse. Neuroscience. 2008;153:329-37 pubmed publisher
    ..The glutamate uptake deficit, moreover, is present in symptomatic HD mice and reversal of this deficit by up-regulating the functional expression of GLT1 with ceftriaxone attenuates the HD phenotype. ..
  46. Liang J, Takeuchi H, Doi Y, Kawanokuchi J, Sonobe Y, Jin S, et al. Excitatory amino acid transporter expression by astrocytes is neuroprotective against microglial excitotoxicity. Brain Res. 2008;1210:11-9 pubmed publisher
    ..These results revealed that astrocytic EAATs can counteract microglial glutamate-induced neuronal death whereas microglial EAATs are inconsequential to neurotoxicity and neuroprotection. ..
  47. Weller M, Stone I, Goss A, Rau T, Rova C, Poulsen D. Selective overexpression of excitatory amino acid transporter 2 (EAAT2) in astrocytes enhances neuroprotection from moderate but not severe hypoxia-ischemia. Neuroscience. 2008;155:1204-11 pubmed publisher
    Attempts have been made to elevate excitatory amino acid transporter 2 (EAAT2) expression in an effort to compensate for loss of function and expression associated with disease or pathology...
  48. Estrada Sánchez A, Montiel T, Segovia J, Massieu L. Glutamate toxicity in the striatum of the R6/2 Huntington's disease transgenic mice is age-dependent and correlates with decreased levels of glutamate transporters. Neurobiol Dis. 2009;34:78-86 pubmed publisher
    ..According to western blot analysis, increased vulnerability to glutamate toxicity correlates with decreased levels of GLT-1 and GLAST glutamate transporters in the striatum. ..
  49. Bradford J, Shin J, Roberts M, Wang C, Li X, Li S. Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms. Proc Natl Acad Sci U S A. 2009;106:22480-5 pubmed publisher
    ..These results imply an important role for glial mutant huntingtin in HD pathology and suggest possibilities for treatment. ..
  50. Weng H, Chen J, Pan Z, Nie H. Glial glutamate transporter 1 regulates the spatial and temporal coding of glutamatergic synaptic transmission in spinal lamina II neurons. Neuroscience. 2007;149:898-907 pubmed
    ..Thus, GLT-1 is a key component in maintaining the spatial and temporal coding in signal transmission at the glutamatergic synapse in substantia gelatinosa neurons. ..
  51. Romera C, Hurtado O, Mallolas J, Pereira M, Morales J, Romera A, et al. Ischemic preconditioning reveals that GLT1/EAAT2 glutamate transporter is a novel PPARgamma target gene involved in neuroprotection. J Cereb Blood Flow Metab. 2007;27:1327-38 pubmed
    ..All these data show that the GLT1/EAAT2 glutamate transporter is a target gene of PPARgamma leading to neuroprotection by increasing glutamate uptake. ..
  52. Omrani A, Melone M, Bellesi M, Safiulina V, Aida T, Tanaka K, et al. Up-regulation of GLT-1 severely impairs LTD at mossy fibre--CA3 synapses. J Physiol. 2009;587:4575-88 pubmed publisher
    ..The enhanced expression of GLT-1 at release sites may prevent activation of presynaptic receptors, thus revealing a novel mechanism by which GLT-1 regulates synaptic plasticity in the hippocampus. ..
  53. 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. ..