Excitatory amino acid transporters: Recent insights into molecular mechanisms, novel modes of modulation and new therapeutic possibilities

Current Opinion in Pharmacology

Volumn 20, Issue , 2015, Pages 116-123

  Jensen, Anders A ^a   Fahlke, Christoph ^b   Bjørn Yoshimoto, Walden E ^a   Bunch, Lennart ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b FORSCHUNGSZENTRUM JÜLICH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANION CHANNEL; EXCITATORY AMINO ACID TRANSPORTER 1; EXCITATORY AMINO ACID TRANSPORTER 2; EXCITATORY AMINO ACID TRANSPORTER 3; EXCITATORY AMINO ACID TRANSPORTER 4; EXCITATORY AMINO ACID TRANSPORTER 5; GLUTAMIC ACID; GLUTAMATE TRANSPORTER;

ALCOHOLISM; ALLOSTERISM; AMINO ACID TRANSPORT; ATAXIA; DEGENERATIVE DISEASE; DRUG ABUSE; DRUG DEPENDENCE; EPILEPSY; HEMIPLEGIA; HUMAN; MENTAL DISEASE; MOLECULAR DYNAMICS; NEUROMODULATION; NEUROTRANSMISSION; NONHUMAN; PAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN STRUCTURE; PROTEIN TRANSPORT; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; CENTRAL NERVOUS SYSTEM; METABOLISM; PHYSIOLOGY; SYNAPTIC TRANSMISSION; TRANSPORT AT THE CELLULAR LEVEL;

ANIMALS; BIOLOGICAL TRANSPORT; CENTRAL NERVOUS SYSTEM; GLUTAMATE PLASMA MEMBRANE TRANSPORT PROTEINS; GLUTAMIC ACID; HUMANS; SYNAPTIC TRANSMISSION;

EID: 84922522810     PISSN: 14714892     EISSN: 14714973     Source Type: Journal    
DOI: 10.1016/j.coph.2014.10.008     Document Type: Review

References (59)

1. N.C. Danbolt Glutamate uptake Prog Neurobiol 65 2001 1 105
2. L. Bunch, M.N. Erichsen, and A.A. Jensen Excitatory amino acid transporters as potential drug targets Expert Opin Ther Targets 13 2009 719 731
3. R.J. Vandenberg, and R.M. Ryan Mechanisms of glutamate transport Physiol Rev 93 2013 1621 1657
4. C. Grewer, A. Gameiro, and T. Rauen SLC1 glutamate transporters Pflugers Arch 466 2014 3 24
5. C. Grewer, P. Balani, C. Weidenfeller, T. Bartusel, Z. Tao, and T. Rauen Individual subunits of the glutamate transporter EAAC1 homotrimer function independently of each other Biochemistry 44 2005 11913 11923
6. H.P. Koch, R.L. Brown, and H.P. Larsson The glutamate-activated anion conductance in excitatory amino acid transporters is gated independently by the individual subunits J Neurosci 27 2007 2943 2947
7. D. Nothmann, A. Leinenweber, D. Torres-Salazar, P. Kovermann, J. Hotzy, A. Gameiro, C. Grewer, and Fahlke Ch Hetero-oligomerization of neuronal glutamate transporters J Biol Chem 286 2011 3935 3943
8. O. Boudker, and G. Verdon Structural perspectives on secondary active transporters Trends Pharmacol Sci 31 2010 418 426
9. N. Reyes, S. Oh, and O. Boudker Binding thermodynamics of a glutamate transporter homolog Nat Struct Mol Biol 20 2013 634 640
10. G. Verdon, S. Oh, R.N. Serio, and O. Boudker Coupled ion binding and structural transitions along the transport cycle of glutamate transporters Elife (Cambridge) 3 2014 e02283
11. G.B. Erkens, I. Hänelt, J.M. Goudsmits, D.J. Slotboom, and A.M. van Oijen Unsynchronised subunit motion in single trimeric sodium-coupled aspartate transporters Nature 502 2013 119 123
12. N. Akyuz, R.B. Altman, S.C. Blanchard, and O. Boudker Transport dynamics in a glutamate transporter homologue Nature 502 2013 114 118
13. J.I. Wadiche, S.G. Amara, and M.P. Kavanaugh Ion fluxes associated with excitatory amino acid transport Neuron 15 1995 721 728
14. W.A. Fairman, R.J. Vandenberg, J.L. Arriza, M.P. Kavanaugh, and S.G. Amara An excitatory amino acid-acid transporter with properties of a ligand-gated chloride channel Nature 375 1995 599 603
15. N. Schneider, S. Cordeiro, J.P. Machtens, S. Braams, T. Rauen, and Ch. Fahlke Functional properties of the retinal glutamate transporters GLT-1c and EAAT5 J Biol Chem 289 2014 1815 1824
16. D.E. Bergles, A.V. Tzingounis, and C.E. Jahr Comparison of coupled and uncoupled currents during glutamate uptake by GLT-1 transporters J Neurosci 22 2002 10153 10162
17. P. Kovermann, J.P. Machtens, D. Ewers, and Ch. Fahlke A conserved aspartate determines pore properties of anion channels associated with excitatory amino acid transporter 4 (EAAT4) J Biol Chem 285 2010 23676 23686
18. C. Mim, P. Balani, T. Rauen, and C. Grewer The glutamate transporter subtypes EAAT4 and EAATs 1-3 transport glutamate with dramatically different kinetics and voltage dependence but share a common uptake mechanism J Gen Physiol 126 2005 571 589
19. M.L. Veruki, S.H. Morkve, and E. Hartveit Activation of a presynaptic glutamate transporter regulates synaptic transmission through electrical signaling Nat Neurosci 9 2006 1388 1396
20. N. Winter, P. Kovermann, and Fahlke Ch A point mutation associated with episodic ataxia 6 increases glutamate transporter anion currents Brain 135 2012 3416 3425
21. A.S. Kristensen, J. Andersen, T.N. Jørgensen, L. Sørensen, J. Eriksen, C.J. Loland, K. Strømgaard, and U. Gether SLC6 neurotransmitter transporters: structure, function, and regulation Pharmacol Rev 63 2011 585 640
22. R. Callender, A. Gameiro, A. Pinto, C. De Micheli, and C. Grewer Mechanism of inhibition of the glutamate transporter EAAC1 by the conformationally constrained glutamate analogue (+)-HIP-B Biochemistry 51 2012 5486 5495
23. 2+ inhibits the anion conductance of the glutamate transporter EAAT4 J Biol Chem 276 2001 26071 26076
24. R.J. Vandenberg, A.D. Mitrovic, and G.A.R. Johnston Molecular basis for differential inhibition of glutamate transporter subtypes by zinc ions Mol Pharmacol 54 1998 189 196
25. S. Habjan, and R.J. Vandenberg Modulation of glutamate and glycine transporters by niflumic, flufenamic and mefenamic acids Neurochem Res 34 2009 1738 1747
26. E. Fumagalli, M. Funicello, T. Rauen, M. Gobbi, and T. Mennini Riluzole enhances the activity of glutamate transporters GLAST, GLT1 and EAAC1 Eur J Pharmacol 578 2008 171 176
27. A.C. Fontana, R. de Oliveira Beleboni, M.W. Wojewodzic, W. Ferreira Dos Santos, J. Coutinho-Netto, N.J. Grutle, S.D. Watts, N.C. Danbolt, and S.G. Amara Enhancing glutamate transport: mechanism of action of Parawixin1, a neuroprotective compound from Parawixia bistriata spider venom Mol Pharmacol 72 2007 1228 1237
28. A.A. Jensen, M.N. Erichsen, C.W. Nielsen, T.B. Stensbøl, J. Kehler, and L. Bunch Discovery of the first selective inhibitor of excitatory amino acid transporter subtype 1 J Med Chem 52 2009 912 915
29. M.N. Erichsen, T.H.V. Huynh, B. Abrahamsen, J.F. Bastlund, C. Bundgaard, O. Monrad, A. Bekker-Jensen, C.W. Nielsen, K. Frydenvang, and A.A. Jensen Structure-activity relationship study of first selective inhibitor of excitatory amino acid transporter subtype 1: 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101) J Med Chem 53 2010 7180 7191
30. B. Abrahamsen, N. Schneider, M.N. Erichsen, T.H. Huynh, Ch. Fahlke, L. Bunch, and A.A. Jensen Allosteric modulation of an excitatory amino acid transporter: the subtype-selective inhibitor UCPH-101 exerts sustained inhibition of EAAT1 through an intramonomeric site in the trimerization domain J Neurosci 33 2013 1068 1087
31. J.D. Rothstein, S. Patel, M.R. Regan, C. Haenggeli, Y.H. Huang, D.E. Bergles, L. Jin, M. Dykes Hoberg, S. Vidensky, and D.S. Chung Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression Nature 433 2005 73 77
32. Y. Li, R. Sattler, E.J. Yang, A. Nunes, Y. Ayukawa, S. Akhtar, G. Ji, P.W. Zhang, and J.D. Rothstein Harmine, a natural beta-carboline alkaloid, upregulates astroglial glutamate transporter expression Neuropharmacology 60 2011 1168 1175
33. C.K. Colton, Q. Kong, L. Lai, M.X. Zhu, K.I. Seyb, G.D. Cuny, J. Xian, M.A. Glicksman, and C.L. Lin Identification of translational activators of glial glutamate transporter EAAT2 through cell-based high-throughput screening: an approach to prevent excitotoxicity J Biomol Screen 15 2010 653 662
34. Q. Kong, L.C. Chang, K. Takahashi, Q. Liu, D.A. Schulte, L. Lai, B. Ibabao, Y. Lin, N. Stouffer, and C. Das Mukhopadhyay Small-molecule activator of glutamate transporter EAAT2 translation provides neuroprotection J Clin Invest 124 2014 1255 1267
35. M.G. Bianchi, R. Franchi-Gazzola, L. Reia, M. Allegri, J. Uggeri, M. Chiu, R. Sala, and O. Bussolati Valproic acid induces the glutamate transporter excitatory amino acid transporter-3 in human oligodendroglioma cells Neuroscience 227 2012 260 270
36. S.G. Lee, Z.Z. Su, L. Emdad, P. Gupta, D. Sarkar, A. Borjabad, D.J. Volsky, and P.B. Fisher Mechanism of ceftriaxone induction of excitatory amino acid transporter-2 expression and glutamate uptake in primary human astrocytes J Biol Chem 283 2008 13116 13123
37. J.E. Kelsey, and C. Neville The effects of the beta-lactam antibiotic, ceftriaxone, on forepaw stepping and L-DOPA-induced dyskinesia in a rodent model of Parkinson's disease Psychopharmacology (Berl) 231 2014 2405 2415
38. Y.S. Mineur, M.R. Picciotto, and G. Sanacora Antidepressant-like effects of ceftriaxone in male C57BL/6J mice Biol Psychiatry 61 2007 250 252
39. Y. Hu, W. Li, L. Lu, J. Cai, X. Xian, M. Zhang, Q. Li, and L. Li An anti-nociceptive role for ceftriaxone in chronic neuropathic pain in rats Pain 148 2010 284 301
40. R.M. Stepanovic-Petrovic, A.M. Micov, M.A. Tomic, J.M. Kovacevic, and B.D. Boskovic Antihyperalgesic/antinociceptive effects of ceftriaxone and its synergistic interactions with different analgesics in inflammatory pain in rodents Anesthesiology 120 2014 737 750
41. H.W. Shen, M.D. Scofield, H. Boger, M. Hensley, and P.W. Kalivas Synaptic glutamate spillover due to impaired glutamate uptake mediates heroin relapse J Neurosci 34 2014 5649 5657
42. K.D. Fischer, A.C. Houston, and G.V. Rebec Role of the major glutamate transporter GLT1 in nucleus accumbens core versus shell in cue-induced cocaine-seeking behavior J Neurosci 33 2013 9319 9327
43. F. Matos-Ocasio, A. Hernandez-Lopez, and K.J. Thompson Ceftriaxone, a GLT-1 transporter activator, disrupts hippocampal learning in rats Pharmacol Biochem Behav 122 2014 118 121
44. J.C. Jen, J. Wan, T.P. Palos, B.D. Howard, and R.W. Baloh Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures Neurology 65 2005 529 534
45. + binding to excitatory amino acid transporters and associated conformational changes J Biol Chem 288 2013 36492 36501
46. S. Holmseth, Y. Dehnes, Y.H. Huang, V.V. Follin-Arbelet, N.J. Grutle, M.N. Mylonakou, C. Plachez, Y. Zhou, D.N. Furness, and D.E. Bergles The density of EAAC1 (EAAT3) glutamate transporters expressed by neurons in the mammalian CNS J Neurosci 32 2012 6000 6013
47. K. Aoyama, S.W. Suh, A.M. Hamby, J. Liu, W.Y. Chan, Y. Chen, and R.A. Swanson Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse Nat Neurosci 9 2006 119 126
48. A.E. Berman, W.Y. Chan, A.M. Brennan, R.C. Reyes, B.L. Adler, S.W. Suh, T.M. Kauppinen, Y. Edling, and R.A. Swanson N-acetylcysteine prevents loss of dopaminergic neurons in the EAAC1-/- mouse Ann Neurol 69 2011 509 520
49. J.D. Rothstein, M. Dykes-Hoberg, C.A. Pardo, L.A. Bristol, L. Jin, R.W. Kuncl, Y. Kanai, M.A. Hediger, Y. Wang, and J.P. Schielke Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate Neuron 16 1996 675 686
50. A. Scimemi, H. Tian, and J.S. Diamond Neuronal transporters regulate glutamate clearance, NMDA receptor activation, and synaptic plasticity in the hippocampus J Neurosci 29 2009 14581 14595
51. L.A. Jarzylo, and H.Y. Man Parasynaptic NMDA receptor signaling couples neuronal glutamate transporter function to AMPA receptor synaptic distribution and stability J Neurosci 32 2012 2552 2563
52. S.M. Underhill, D.S. Wheeler, M. Li, S.D. Watts, S.L. Ingram, and S.G. Amara Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons Neuron 83 2014 404 416
53. Y. Jong, V. Kumar, A.E. Kingston, C. Romano, and K.L. O'Malley Functional metabotropic glutamate receptors on nuclei from brain and primary cultured striatal neurons: role of transporters in delivering ligand J Biol Chem 280 2005 30469 30480
54. C.A. Purgert, Y. Izumi, Y.J. Jong, V. Kumar, C.F. Zorumski, and K.L. O'Malley Intracellular mGluR5 can mediate synaptic plasticity in the hippocampus J Neurosci 34 2014 4589 4598
55. D. Ewers, T. Becher, J.P. Machtens, I. Weyand, and Ch. Fahlke Induced fit substrate binding to an archeal glutamate transporter homologue Proc Natl Acad Sci U S A 110 2013 12486 12491
56. P.J. Focke, P. Moenne-Loccoz, and H.P. Larsson Opposite movement of the external gate of a glutamate transporter homolog upon binding cotransported sodium compared with substrate J Neurosci 31 2011 6255 6262
57. N. Reyes, C. Ginter, and O. Boudker Transport mechanism of a bacterial homologue of glutamate transporters Nature 462 2009 880 885
58. E.R. Georgieva, P.P. Borbat, C. Ginter, J.H. Freed, and O. Boudker Conformational ensemble of the sodium-coupled aspartate transporter Nat Struct Mol Biol 20 2013 215 221
59. Ph Nat Struct Mol Biol 20 2013 210 214