excitatory amino acid transporter 3

Summary

Summary: A neuronal and epithelial type glutamate plasma membrane transporter protein.

Top Publications

  1. Furuta A, Martin L, Lin C, Dykes Hoberg M, Rothstein J. Cellular and synaptic localization of the neuronal glutamate transporters excitatory amino acid transporter 3 and 4. Neuroscience. 1997;81:1031-42 pubmed
    ..Both neuronal glutamate transporter EAAT3 (EAAC1) and EAAT4 are located at somatodendritic compartment of Purkinje cells, and probably contribute to glutamate re-uptake mechanisms at Purkinje cell synapses. ..
  2. Medina Ceja L, Sandoval García F, Pardo Peña K. Effect of early glutamate exposure on EAAT-3 and GAT-1 protein expression in cells of the dentate gyrus and CA1 region of the adult rat hippocampus. Arch Med Res. 2011;42:433-8 pubmed publisher
  3. 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. ..
  4. Deng X, Shibata H, Takeuchi N, Rachi S, Sakai M, Ninomiya H, et al. Association study of polymorphisms in the glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 with schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:271-8 pubmed
    ..031). We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby SLC1A6, whereas SLC1A1 and SLC1A3 are unlikely to be major susceptibility genes for schizophrenia in the Japanese population. ..
  5. Horiuchi Y, Iida S, Koga M, Ishiguro H, Iijima Y, Inada T, et al. Association of SNPs linked to increased expression of SLC1A1 with schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2012;159B:30-7 pubmed publisher
    ..003). Our findings suggest the involvement of SLC1A1 in the pathogenesis of schizophrenia. ..
  6. Ryu S, Oh S, Cho E, Nam H, Yoo J, Park T, et al. Interaction between genetic variants of DLGAP3 and SLC1A1 affecting the risk of atypical antipsychotics-induced obsessive-compulsive symptoms. Am J Med Genet B Neuropsychiatr Genet. 2011;156B:949-59 pubmed publisher
    ..This study provides suggestive evidence that DLGAP3 and its interactive effect with SLC1A1 might be involved in susceptibility to developing OC symptoms in schizophrenia patients receiving AAP treatment. ..
  7. Stewart S, Fagerness J, Platko J, Smoller J, Scharf J, Illmann C, et al. Association of the SLC1A1 glutamate transporter gene and obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:1027-33 pubmed
    ..045). This study identifies a significant association between the SLC1A1 glutamate transporter gene and OCD in a haplotype overlapping with that recently reported. ..
  8. Lin C, Orlov I, Ruggiero A, Dykes Hoberg M, Lee A, Jackson M, et al. Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18. Nature. 2001;410:84-8 pubmed
    ..These studies show that glutamate transport proteins can be regulated potently and that GTRAP can modulate the transport functions ascribed to EAAC1. GTRAP3-18 may be important in regulating the metabolic function of EAAC1...
  9. Shugart Y, Wang Y, Samuels J, Grados M, Greenberg B, Knowles J, et al. A family-based association study of the glutamate transporter gene SLC1A1 in obsessive-compulsive disorder in 378 families. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:886-92 pubmed publisher
    ..5 kb away from the boundary of the SLC1A1 gene. However, this potential finding needs to be validated biologically. Further functional studies in this region are planned by this research group. ..

More Information

Publications62

  1. Scimemi A, Tian H, Diamond J. Neuronal transporters regulate glutamate clearance, NMDA receptor activation, and synaptic plasticity in the hippocampus. J Neurosci. 2009;29:14581-95 pubmed publisher
    ..We describe novel roles of EAAC1 in regulating glutamate diffusion and propose that NMDARs at different subsynaptic locations can make distinct contributions to the regulation of synaptic strength. ..
  2. Schirmbeck F, Nieratschker V, Frank J, Englisch S, Rausch F, Meyer Lindenberg A, et al. Polymorphisms in the glutamate transporter gene SLC1A1 and obsessive-compulsive symptoms induced by second-generation antipsychotic agents. Psychiatr Genet. 2012;22:245-52 pubmed publisher
    ..In contrast to the Asian sample, no genetic associations were found with OCS. Larger samples are necessary to unravel the interplay of pharmacological and genetic risk factors for OCS in schizophrenia. ..
  3. Dickel D, Veenstra Vanderweele J, Cox N, Wu X, Fischer D, Van Etten Lee M, et al. Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder. Arch Gen Psychiatry. 2006;63:778-85 pubmed
    ..The results also provide further support for the involvement of a glutamatergic dysfunction in the pathogenesis of early-onset OCD. ..
  4. 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
  5. Samuels J, Wang Y, Riddle M, Greenberg B, Fyer A, McCracken J, et al. Comprehensive family-based association study of the glutamate transporter gene SLC1A1 in obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet. 2011;156B:472-7 pubmed publisher
    ..00015) and in families with male affecteds (P = 0.0007). Although of nominal statistical significance considering the number of comparisons, these findings provide further support for the involvement of SLC1A1 in the pathogenesis of OCD. ..
  6. Crino P, Jin H, Shumate M, Robinson M, Coulter D, Brooks Kayal A. Increased expression of the neuronal glutamate transporter (EAAT3/EAAC1) in hippocampal and neocortical epilepsy. Epilepsia. 2002;43:211-8 pubmed
    ..Upregulation of EAAT3/EAAC1 in hippocampal and neocortical epilepsy may be an important modulator of extracellular glutamate concentrations and may occur as a response to recurrent seizures in these cell types. ..
  7. Yu Y, Shen L, Xia P, Tang Y, Bao L, Pei G. Syntaxin 1A promotes the endocytic sorting of EAAC1 leading to inhibition of glutamate transport. J Cell Sci. 2006;119:3776-87 pubmed
    ..These findings provide new evidence that syntaxin 1A serves as an intrinsic enhancer to EAAC1 endocytic sorting and further suggest that syntaxin 1A is conversant with both ;ins' and ;outs' of synaptic neurotransmission. ..
  8. Menaker D, Bendahan A, Kanner B. The substrate specificity of a neuronal glutamate transporter is determined by the nature of the coupling ion. J Neurochem. 2006;99:20-8 pubmed
    ..Our results indicate that, subsequent to substrate binding, the co-transported solutes interact functionally in the binding pocket of the transporter. ..
  9. Lee A, Anderson A, Barnett A, Chan A, Pow D. Expression of multiple glutamate transporter splice variants in the rodent testis. Asian J Androl. 2011;13:254-65 pubmed publisher
    ..The apparent presence of many of these transporters in the testis and sperm may indicate a need for glutamate transport by such cells. ..
  10. 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. ..
  11. Grewer C, Watzke N, Wiessner M, Rauen T. Glutamate translocation of the neuronal glutamate transporter EAAC1 occurs within milliseconds. Proc Natl Acad Sci U S A. 2000;97:9706-11 pubmed
  12. Wendland J, Moya P, Timpano K, Anavitarte A, Kruse M, Wheaton M, et al. A haplotype containing quantitative trait loci for SLC1A1 gene expression and its association with obsessive-compulsive disorder. Arch Gen Psychiatry. 2009;66:408-16 pubmed publisher
    ..The expression and genotype database-mining approach we used provides a potentially useful complementary approach to strengthen future candidate gene studies in neuropsychiatric and other disorders. ..
  13. Escartin C, Won S, Malgorn C, Auregan G, Berman A, Chen P, et al. Nuclear factor erythroid 2-related factor 2 facilitates neuronal glutathione synthesis by upregulating neuronal excitatory amino acid transporter 3 expression. J Neurosci. 2011;31:7392-401 pubmed publisher
    ..Free cysteine is then taken up by neurons through excitatory amino acid transporter 3 [EAAT3; also termed Slc1a1 (solute carrier family 1 member 1)] to support de novo glutathione ..
  14. Kwon J, Joo Y, Nam H, Lim M, Cho E, Jung M, et al. Association of the glutamate transporter gene SLC1A1 with atypical antipsychotics-induced obsessive-compulsive symptoms. Arch Gen Psychiatry. 2009;66:1233-41 pubmed publisher
    ..This is the first published pharmacogenetic study on this phenomenon and provides preliminary evidence of the involvement of glutamatergic neurotransmission in the pathogenesis of AAP-induced OC symptoms. ..
  15. Gadow K, Roohi J, DeVincent C, Kirsch S, Hatchwell E. Glutamate transporter gene (SLC1A1) single nucleotide polymorphism (rs301430) and repetitive behaviors and anxiety in children with autism spectrum disorder. J Autism Dev Disord. 2010;40:1139-45 pubmed publisher
    ..Allelic variation in SLC1A1 may be a biomarker for or modifier of anxiety symptom severity in children with ASD, but study findings are best conceptualized as tentative pending replication with larger independent samples. ..
  16. Arnold P, Sicard T, Burroughs E, Richter M, Kennedy J. Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Arch Gen Psychiatry. 2006;63:769-76 pubmed
    ..Furthermore, these results provide support for the role of altered glutamatergic neurotransmission in the pathogenesis of OCD. ..
  17. Cheng C, Glover G, Banker G, Amara S. A novel sorting motif in the glutamate transporter excitatory amino acid transporter 3 directs its targeting in Madin-Darby canine kidney cells and hippocampal neurons. J Neurosci. 2002;22:10643-52 pubmed
    The glutamate transporter excitatory amino acid transporter 3 (EAAT3) is polarized to the apical surface in epithelial cells and localized to the dendritic compartment in hippocampal neurons, where it is clustered adjacent to ..
  18. Grewer C, Watzke N, Rauen T, Bicho A. Is the glutamate residue Glu-373 the proton acceptor of the excitatory amino acid carrier 1?. J Biol Chem. 2003;278:2585-92 pubmed
    ..The function of alanine-serine-cysteine transporter is neither potassium- nor proton-dependent. Consequently, our results emphasize the general importance of glutamate and aspartate residues for proton transport across membranes. ..
  19. Zerangue N, Kavanaugh M. Interaction of L-cysteine with a human excitatory amino acid transporter. J Physiol. 1996;493 ( Pt 2):419-23 pubmed
    ..5. Because the EAAT3 transporter is also expressed in tissues including kidney and intestine, the results suggest the possibility of a heretofore unrecognized mechanism of L-cysteine uptake in peripheral tissues as well as in brain. ..
  20. Fournier K, Gonzalez M, Robinson M. Rapid trafficking of the neuronal glutamate transporter, EAAC1: evidence for distinct trafficking pathways differentially regulated by protein kinase C and platelet-derived growth factor. J Biol Chem. 2004;279:34505-13 pubmed
    ..The data also suggest that basal and regulated pools of EAAC1 exist in distinct compartments. ..
  21. 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. ..
  22. Sepkuty J, Cohen A, Eccles C, Rafiq A, Behar K, Ganel R, et al. A neuronal glutamate transporter contributes to neurotransmitter GABA synthesis and epilepsy. J Neurosci. 2002;22:6372-9 pubmed
    ..EAAC1 may participate in normal GABA neurosynthesis and limbic hyperexcitability, whereas epilepsy can result from a disruption of the interaction between EAAC1 and GABA metabolism. ..
  23. Sheldon A, Gonzalez M, Robinson M. A carboxyl-terminal determinant of the neuronal glutamate transporter, EAAC1, is required for platelet-derived growth factor-dependent trafficking. J Biol Chem. 2006;281:4876-86 pubmed
    ..These studies identify a novel motif within the carboxyl terminus of EAAC1 which is required for regulated trafficking. The possibility that this motif targets EAAC1 to an intracellular, "regulated pool" is discussed. ..
  24. Holmseth S, Dehnes Y, Bjørnsen L, Boulland J, Furness D, Bergles D, et al. Specificity of antibodies: unexpected cross-reactivity of antibodies directed against the excitatory amino acid transporter 3 (EAAT3). Neuroscience. 2005;136:649-60 pubmed
    ..Here we illustrate this by describing the production and characterization of antibodies to excitatory amino acid transporter 3 (EAAT3)...
  25. Grewer C, Balani P, Weidenfeller C, Bartusel T, Tao Z, Rauen T. Individual subunits of the glutamate transporter EAAC1 homotrimer function independently of each other. Biochemistry. 2005;44:11913-23 pubmed
    ..In conclusion, we propose that EAAC1 assembles as trimers of identical subunits but that the individual subunits in the trimer function independently of each other. ..
  26. Ross J, Porter B, Buckley P, Eberwine J, Robinson M. mRNA for the EAAC1 subtype of glutamate transporter is present in neuronal dendrites in vitro and dramatically increases in vivo after a seizure. Neurochem Int. 2011;58:366-75 pubmed publisher
    ..These studies provide the first evidence that EAAC1 mRNA localizes to dendrites and suggest that dendritic targeting of EAAC1 mRNA is increased by seizure activity and may be regulated by neuronal activity/depolarization. ..
  27. Holmseth S, Dehnes Y, Huang Y, Follin Arbelet V, Grutle N, Mylonakou M, et al. The density of EAAC1 (EAAT3) glutamate transporters expressed by neurons in the mammalian CNS. J Neurosci. 2012;32:6000-13 pubmed publisher
    ..These findings raise new questions about how so few transporters can influence the activation of NMDA receptors at excitatory synapses. ..
  28. D Amico A, Soragna A, Di Cairano E, Panzeri N, Anzai N, Vellea Sacchi F, et al. The surface density of the glutamate transporter EAAC1 is controlled by interactions with PDZK1 and AP2 adaptor complexes. Traffic. 2010;11:1455-70 pubmed publisher
    ..We suggest that EAAC1 density is controlled by balanced interactions with PDZK1 and adaptor protein 2 (AP2): the former promotes the transporter expression at the cell surface, and the latter mediates its constitutive endocytosis. ..
  29. Brune C, Kim S, Hanna G, Courchesne E, Lord C, Leventhal B, et al. Family-Based Association Testing of OCD-associated SNPs of SLC1A1 in an autism sample. Autism Res. 2008;1:108-13 pubmed publisher
    ..01). The G allele was also undertransmitted in the T-G haplotype under the recessive model (Z=-2.41, P=0.02). Both findings were also observed in the male-only sample. However, they did not withstand correction for multiple comparisons. ..
  30. 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
  31. Jin X, Peng J, Huang F, Zhu Y, Fei J, Guo L. A mRNA molecule encoding truncated excitatory amino acid carrier 1 (EAAC1) protein (EAAC2) is transcribed from an independent promoter but not an alternative splicing event. Cell Res. 2002;12:257-62 pubmed
    ..These results indicate that EAAC2 is transcribed from an independent promoter but not an alternative splicing event. ..
  32. 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. ..
  33. 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
  34. 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. ..
  35. Watabe M, Aoyama K, Nakaki T. A dominant role of GTRAP3-18 in neuronal glutathione synthesis. J Neurosci. 2008;28:9404-13 pubmed publisher
    ..Our results demonstrate GTRAP3-18 to dominantly and negatively determine the intracellular glutathione contents in neurons. ..
  36. Gonzalez M, Kazanietz M, Robinson M. Regulation of the neuronal glutamate transporter excitatory amino acid carrier-1 (EAAC1) by different protein kinase C subtypes. Mol Pharmacol. 2002;62:901-10 pubmed
    ..The potential relationship of the present work with a previously identified role for PKCalpha in certain forms of synaptic plasticity is discussed. ..
  37. Josephson E, Morest D. Synaptic nests lack glutamate transporters in the cochlear nucleus of the mouse. Synapse. 2003;49:29-46 pubmed
    ..Consequently, synaptic nests may play a role in modulation of synaptic activity but also in excitotoxic mechanisms. ..
  38. Perego C, Di Cairano E, Ballabio M, Magnaghi V. Neurosteroid allopregnanolone regulates EAAC1-mediated glutamate uptake and triggers actin changes in Schwann cells. J Cell Physiol. 2012;227:1740-51 pubmed publisher
    ..Glutamate transporters may represent a potential therapeutic target to control Schwann cell physiology. ..
  39. Huang Y, Zuo Z. Isoflurane induces a protein kinase C alpha-dependent increase in cell-surface protein level and activity of glutamate transporter type 3. Mol Pharmacol. 2005;67:1522-33 pubmed
    ..the commonly used anesthetic isoflurane increased the activity of glutamate transporter type 3 (excitatory amino acid transporter 3, EAAT3) possibly via a protein kinase C (PKC)-dependent pathway...
  40. Bailey C, Ryan R, Thoeng A, Ng C, KING K, Vanslambrouck J, et al. Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. J Clin Invest. 2011;121:446-53 pubmed publisher
    ..These findings provide evidence that SLC1A1 is the major renal transporter of glutamate and aspartate in humans and implicate SLC1A1 in the pathogenesis of some neurological disorders. ..
  41. Tai Y, Wang Y, Tsai R, Wang J, Tao P, Liu T, et al. Amitriptyline preserves morphine's antinociceptive effect by regulating the glutamate transporter GLAST and GLT-1 trafficking and excitatory amino acids concentration in morphine-tolerant rats. Pain. 2007;129:343-54 pubmed
  42. Mott C, Siegel P, Webb K, Wong E. Gene expression of nutrient transporters in the small intestine of chickens from lines divergently selected for high or low juvenile body weight. Poult Sci. 2008;87:2215-24 pubmed publisher
  43. van Landeghem F, Weiss T, von Deimling A. Expression of PACAP and glutamate transporter proteins in satellite oligodendrocytes of the human CNS. Regul Pept. 2007;142:52-9 pubmed
    ..Further studies should clarify whether these alterations in protein expression are primary or secondary to neuronal cell death. ..
  44. Huang Y, Li L, Washington J, Xu X, Sando J, Lin D, et al. Inhibition of isoflurane-induced increase of cell-surface redistribution and activity of glutamate transporter type 3 by serine 465 sequence-specific peptides. Eur J Pharmacol. 2011;655:16-22 pubmed publisher
    ..The S465 sequence-specific peptide may interrupt this interaction and is an effective inhibitor for the regulation of EAAT3 activity and trafficking by PKC? and isoflurane. ..
  45. 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. ..
  46. Vera Portocarrero L, Mills C, Ye Z, Fullwood S, McAdoo D, Hulsebosch C, et al. Rapid changes in expression of glutamate transporters after spinal cord injury. Brain Res. 2002;927:104-10 pubmed
    ..The results suggest that upregulation of these high affinity transporters occurs rapidly and is important in regulating glutamate homeostasis after SCI. ..
  47. Jackson M, Song W, Liu M, Jin L, Dykes Hoberg M, Lin C, et al. Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins. Nature. 2001;410:89-93 pubmed
  48. Baik H, Lee S, Washington J, Zuo Z. Amitriptyline inhibits the activity of the rat glutamate transporter EAAT3 expressed in Xenopus oocytes. J Pharm Pharmacol. 2009;61:577-81 pubmed publisher
    ..Protein kinase C may not have been involved in the effects of amitriptyline on EAAT3. ..
  49. Zhang Z, Tao Z, Gameiro A, Barcelona S, Braams S, Rauen T, et al. Transport direction determines the kinetics of substrate transport by the glutamate transporter EAAC1. Proc Natl Acad Sci U S A. 2007;104:18025-30 pubmed
    ..Our model can be used to predict rates of glutamate release from neurons under physiological and pathophysiological conditions. ..
  50. Mishra M, Singh R, Mukherjee S, Sharma D. Dehydroepiandrosterone's antiepileptic action in FeCl3-induced epileptogenesis involves upregulation of glutamate transporters. Epilepsy Res. 2013;106:83-91 pubmed publisher
    ..The results are of significance in respect of the mechanism of the antiepileptic action of neurosteroids and the glutamate transporters as therapeutic targets in glutamatergic epileptogenesis. ..
  51. Aoyama K, Nakaki T. Glutathione in Cellular Redox Homeostasis: Association with the Excitatory Amino Acid Carrier 1 (EAAC1). Molecules. 2015;20:8742-58 pubmed publisher
    ..Excitatory amino acid carrier 1 (EAAC1) plays a pivotal role in neuronal GSH synthesis. The regulatory mechanism of EAAC1 is also discussed. ..
  52. Dong L, Winkelstein B. Simulated whiplash modulates expression of the glutamatergic system in the spinal cord suggesting spinal plasticity is associated with painful dynamic cervical facet loading. J Neurotrauma. 2010;27:163-74 pubmed publisher
  53. Collin M, Bäckberg M, Ovesjö M, Fisone G, Edwards R, Fujiyama F, et al. Plasma membrane and vesicular glutamate transporter mRNAs/proteins in hypothalamic neurons that regulate body weight. Eur J Neurosci. 2003;18:1265-78 pubmed
    ..glutamate is taken up by the nerve terminal via a plasma membrane-associated protein termed excitatory amino acid transporter 3 (EAAT3)...