Glutamate forward and reverse transport: From molecular mechanism to transporter-mediated release after ischemia

IUBMB Life

Volumn 60, Issue 9, 2008, Pages 609-619

  Grewer, Christof ^a   Gameiro, Armanda ^a   Zhang, Zhou ^a,c   Tao, Zhen ^a,d   Braams, Simona ^b   Rauen, Thomas ^b  

^a BINGHAMTON UNIVERSITY   (United States)

^b UNIVERSITY OF OSNABRÜCK   (Germany)

^c SHANGHAI NORMAL UNIVERSITY   (China)

^d YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Electrophysiology; Glutamate release; Glutamate transporter; Kinetics; Reverse transport; Transport mechanism

Indexed keywords

GLUTAMATE TRANSPORTER; GLUTAMIC ACID;

BINDING SITE; BRAIN ISCHEMIA; CATION TRANSPORT; CELL FUNCTION; DISEASE ASSOCIATION; HUMAN; ION CONDUCTANCE; MEMBRANE TRANSPORT; MOLECULAR MECHANICS; PHYSIOLOGICAL PROCESS; REVIEW; TRANSPORT KINETICS; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; GENETICS; METABOLISM; NERVE CELL; PHYSIOLOGY; PROTEIN CONFORMATION; SYNAPSE; TRANSPORT AT THE CELLULAR LEVEL;

AMINO ACID TRANSPORT SYSTEM X-AG; ANIMALS; BINDING SITES; BIOLOGICAL TRANSPORT; BRAIN ISCHEMIA; GLUTAMIC ACID; MODELS, MOLECULAR; NEURONS; PROTEIN CONFORMATION; SYNAPSES;

EID: 56149119337     PISSN: 15216543     EISSN: 15216551     Source Type: Journal    
DOI: 10.1002/iub.98     Document Type: Review

References (86)

1. Danbolt, N. C. (2001) Glutamate uptake. Prog. Neurobiol. 65, 101-105.
2. Grewer, C., and Rauen, T. (2005) electrogenic glutamate transporters in the cns: molecular mechanism, pre-steady-state kinetics, and their impact on synaptic signaling. J. Membr. Biol. 203, 1-20.
3. Sheldon, A. L., and Robinson, M. B. (2007) The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention. Neurochem. Int. 51, 333-355.
4. Vandenberg, R. J. (1998) Molecular pharmacology and physiology of glutamate transporters in the central nervous system. Clin. Exp. Pharmacol. Physiol. 25, 393-400.
5. Kanai, Y., and Hediger, M. A. (2003) The glutamate and neutral amino acid transporter family: physiological and pharmacological implications. Eur. J. Pharmacol. 479, 237-247.
6. Hertz, L. (1979) Functional interactions between neurons and astrocytes I. Turnover and metabolism of putative amino acid transmitters. Prog. Neurobiol. 13, 277-323.
7. Albrecht, J., Sonnewald, U., Waagepetersen, H. S., and Schousboe, A. (2007) Glutamine in the central nervous system: function and dysfunction. Front. Biosci. 12, 332-343.
8. Bellocchio, E. E., Reimer, R. J., Fremeau, R. T., Jr., and Edwards, R. H. (2000) Uptake of glutamate into synaptic vesicles by an inorganic phosphate transporter. Science 289, 957-960. (Pubitemid 30659949)
9. Takamori, S., Rhee, J. S., Rosenmund, C., and Jahn, R. (2000) Identification of a vesicular glutamate transporter that defines a glutamatergic phenotype in neurons. Nature 407, 189-194.
10. Hediger, M. A., Romero, M. F., Peng, J. B., Rolfs, A., Takanaga, H., and Bruford, E. A. (2004) The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteinsIntroduction. Pflugers Arch. Eur. J. Phyiol. 447, 465-468.
11. Kanner, B. I., and Sharon, I. (1978) Active transport of L-glutamate by membrane vesicles isolated from rat brain. Biochemistry 17, 3949-3953. (Pubitemid 9036507)
12. Levy, L. M., Warr, O., and Attwell, D. (1998) Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. J. Neurosci. 18, 9620-9628. (Pubitemid 28543743)
13. Owe, S. G., Marcaggi, P., and Attwell, D. (2006) The ionic stoichiometry of the GLAST glutamate transporter in salamander retinal glia. J. Physiol. 577, 591-599. (Pubitemid 44804015)
14. Zerangue, N., and Kavanaugh, M. P. (1996) Flux coupling in a neuronal glutamate transporter. Nature 383, 634-637. (Pubitemid 26347587)
15. Kanner, B. I., and Bendahan, A. (1982) Binding order of substrates to the sodium and potassium ion coupled L-glutamic acid transporter from rat brain. Biochemistry 21, 6327-6330.
16. Wadiche, J. I., Amara, S. G., and Kavanaugh, M. P. (1995) Ion fluxes associated with excitatory amino acid transport. Neuron 15, 721-728.
17. Picaud, S. A., Larsson, H. P., Grant, G. B., Lecar, H., and Werblin, F. S. (1995) Glutamate-gated chloride channel with glutamate-transporterlike properties in cone photoreceptors of the tiger salamander. J. Neurophysiol. 74, 1760-1771.
18. Eliasof, S., and Jahr, C. E. (1996) Retinal glial cell glutamate transporter is coupled to an anionic conductance. Proc. Natl. Acad. Sci. USA 93, 4153-4158.
19. Eskandari, S., Kreman, M., Kavanaugh, M. P., Wright, E. M., and Zampighi, G. A. (2000) Pentameric assembly of a neuronal glutamate transporter. Proc. Natl. Acad. Sci. USA 97, 8641-8646.
20. Grewer, C., Balani, P., Weidenfeller, C., Bartusel, T., Tao, Z., and Rauen, T. (2005) Individual subunits of the glutamate transporter EAAC1 homotrimer function independently of each other. Biochemistry 44, 11913-11923. (Pubitemid 41262726)
21. Leary, G. P., Stone, E. F., Holley, D. C., and Kavanaugh, M. P. (2007) The glutamate and chloride permeation pathways are colocalized in individual neuronal glutamate transporter subunits. J. Neurosci. 27, 2938-2942.
22. Koch, H. P., Lane Brown, R., and Larsson, H. P. (2007) The glutamateactivated anion conductance in excitatory amino acid transporters is gated independently by the individual subunits. J. Neurosci. 27, 2943-2947.
23. Wadiche, J. I., and Kavanaugh, M. P. (1998) Macroscopic and microscopic properties of a cloned glutamate transporter/chloride channel. J. Neurosci. 18, 7650-7661.
24. Melzer, N., Biela, A., and Fahlke, C. (2003) Glutamate modifies ion conduction and voltage-dependent gating of excitatory amino acid transporter- associated anion channels. J. Biol. Chem. 278, 50112-50119.
25. Broer, A., Wagner, C., Lang, F., and Broer, S. (2000) Neutral amino acid transporter ASCT2 displays substrate-induced Na+ exchange and a substrate-gated anion conductance. Biochem. J. 346, 705-710. (Pubitemid 30171031)
26. Grewer, C., and Grabsch, E. (2004) New inhibitors for the neutral amino acid transporter ASCT2 reveal its Na+-dependent anion leak. J. Physiol. 557, 747-759. (Pubitemid 38961613)
27. Ryan, R. M., and Mindell, J. A. (2007) The uncoupled chloride conductance of a bacterial glutamate transporter homolog. Nat. Struct. Mol. Biol. 14, 365-371.
28. Fairman, W. A., Vandenberg, R. J., Arriza, J. L., Kavanaugh, M. P., and Amara, S. G. (1995) An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature 375, 599-603.
29. Kanai, Y., and Hediger, M. A. (1992) Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 360, 467-471.
30. Pines, G., Danbolt, N. C., Bjoras, M., Zhang, Y., Bendahan, A., Eide, L., Koepsell, H., Storm Mathisen, J., Seeberg, E., and Kanner, B. I. (1992) Cloning and expression of a rat brain l glutamate transporter. Nature 360, 464-467.
31. Storck, T., Schulte, S., Hofmann, K., and Stoffel, W. (1992) Structure, expression, and functional analysis of a Na(+)-dependent glutamate/ aspartate transporter from rat brain. Proc. Natl. Acad. Sci. USA 89, 10955-10959.
32. Yernool, D., Boudker, O., Jin, Y., and Gouaux, E. (2004) Structure of a glutamate transporter homologue from pyrococcus horikoshii. Nature 431, 811-818. (Pubitemid 39434071)
33. Grunewald, M., and Kanner, B. I. (2000) The accessibility of a novel reentrant loop of the glutamate transporter GLT-1 is restricted by its substrate. J. Biol. Chem. 275, 9684-9689.
34. Slotboom, D. J., Sobczak, I., Konings, W. N., and Lolkema, J. S. (1999) A conserved serine-rich stretch in the glutamate transporter family forms a substrate-sensitive reentrant loop. Proc. Natl. Acad. Sci. USA 96, 14282-14287.
35. Gendreau, S., Voswinkel, S., Torres-Salazar, D., Lang, N., Heidtmann, H., Detro-Dassen, S., Schmalzing, G., Hidalgo, P., and Fahlke, C. (2004) A trimeric quaternary structure is conserved in bacterial and human glutamate transporters. J. Biol. Chem. 279, 39505-39512.
36. Bendahan, A., Armon, A., Madani, N., Kavanaugh, M. P., and Kanner B. I. (2000) Arginine 447 plays a pivotal role in substrate interactions in a neuronal glutamate transporter. J. Biol. Chem. 275, 37436-37442.
37. Teichman, S., and Kanner, B. I. (2007) Aspartate-444 is essential for productive substrate interactions in a neuronal glutamate transporter. J. Gen. Physiol. 129, 527-539.
38. Koch, H. P., and Larsson, H. P. (2005) Small-scale molecular motions accomplish glutamate uptake in human glutamate transporters. J. Neurosci. 25, 1730-1736.
39. Torres-Salazar, D., and Fahlke, C. (2006) Intersubunit interactions in EAAT4 glutamate transporters. J. Neurosci. 26, 7513-7522. (Pubitemid 44315220)
40. Koch, H. P., Hubbard, J. M., and Larsson, H. P. (2007) Voltage-independent sodium-binding events reported by the 4B-4C loop in the human glutamate transporter EAAT3. J. Biol. Chem. 282, 24547-24553.
41. Boudker, O., Ryan, R. M., Yernool, D., Shimamoto, K., and Gouaux, E. (2007) Coupling substrate and ion binding to extracellular gate of a sodium- dependent aspartate transporter. Nature 445, 387-393. (Pubitemid 46160902)
42. Tao, Z., Zhang, Z., and Grewer, C. (2006) 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. 281, 10263-10272.
43. Tao, Z., and Grewer, C. (2007) Cooperation of the conserved aspartate 439 and bound amino acid substrate is important for high-affinity Na+ binding to the glutamate transporter EAAC1. J. Gen. Physiol. 129, 331-344.
44. Kavanaugh, M. P., Bendahan, A., Zerangue, N., Zhang, Y., and Kanner, B. I. (1997) Mutation of an amino acid residue influencing potassium coupling in the glutamate transporter GLT-1 induces obligate exchange. J.Biol. Chem. 272, 1703-1708.
45. Zarbiv, R., Grunewald, M., Kavanaugh, M. P., and Kanner, B. I. (1998) Cysteine scanning of the surroundings of an alkali-ion binding site of the glutamate transporter GLT-1 reveals a conformationally sensitive residue. J. Biol. Chem. 273, 14231-14237.
46. Zhang, Y., and Kanner, B. I. (1999) Two serine residues of the glutamate transporter GLT-1 are crucial for coupling the fluxes of sodium and the neurotransmitter. Proc. Natl. Acad. Sci. USA 96, 1710-1715.
47. Rosental, N., Bendahan, A., and Kanner, B. I. (2006) Multiple consequences of mutating two conserved beta-bridge forming residues in the translocation cycle of a neuronal glutamate transporter. J. Biol. Chem. 281, 27905-27915.
48. Jardetzky, O. (1966) Simple allosteric model for membrane pumps. Nature 211, 969-970.
49. Kanner, B. I. (2007) Gate movements in glutamate transporters. ACS Chem. Biol. 2, 163-166.
50. Otis, T. S., and Kavanaugh, M. P. (2000) Isolation of current components and partial reaction cycles in the glial glutamate transporter EAAT2. J. Neurosci. 20, 2749-2757.
51. Auger, C., and Attwell, D. (2000) Fast removal of synaptic glutamate by postsynaptic transporters. Neuron 28, 547-558.
52. Bergles, D. E., Tzingounis, A. V., and Jahr, C. E. (2002) Comparison of coupled and uncoupled currents during glutamate uptake by GLT-1 transporters. J. Neurosci. 22, 10153-10162
53. Watzke, N., Bamberg, E., and Grewer, C. (2001) Early intermediates in the transport cycle of the neuronal excitatory amino acid carrier EAAC1. J. Gen. Physiol. 117, 547-562.
54. Mim, C., Balani, P., Rauen, T., and Grewer, C. (2005) 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, 571-589.
55. Mim, C., Tao, Z., and Grewer, C. (2007) Two conformational changes are associated with glutamate translocation by the glutamate transporter EAAC1. Biochemistry 46, 9007-9018. (Pubitemid 47237376)
56. Shlaifer, I., and Kanner, B. I. (2007) Conformationally sensitive reactivity to permeant sulfhydryl reagents of cysteine residues engineered into helical hairpin 1 of the glutamate transporter GLT-1. Mol. Pharmacol. 71, 1341-1348.
57. Brocke, L., Bendahan, A., Grunewald, M., and Kanner, B. I. (2002) Proximity of two oppositely oriented reentrant loops in the glutamate transporter GLT-1 identified by paired cysteine mutagenesis. J. Biol. Chem. 277, 3985-3992.
58. Leighton, B. H., Seal, R. P., Watts, S. D., Skyba, M. O., and Amara, S. G. (2006) Structural rearrangements at the translocation pore of the human glutamate transporter, EAAT1. J. Biol. Chem. 281, 29788-29796.
59. Szatkowski, M., Barbour, B., and Attwell, D. (1990) Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptake. Nature 348, 443-446. (Pubitemid 120015084)
60. Billups, B., and Attwell, D. (1996) Modulation of non-vesicular glutamate release by pH. Nature 379, 171-174.
61. Jabaudon, D., Scanziani, M., Gahwiler, B. H., and Gerber, U. (2000) Acute decrease in net glutamate uptake during energy deprivation. Proc. Natl. Acad. Sci. USA 97, 5610-5615.
62. Watzke, N., and Grewer, C. (2001) The anion conductance of the glutamate transporter EAAC1 depends on the direction of glutamate transport. FEBS Lett. 503, 121-125. (Pubitemid 32763190)
63. Watzke, N., Rauen, T., Bamberg, E., and Grewer, C. (2000) On the mechanism of proton transport by the neuronal excitatory amino acid carrier 1. J. Gen. Physiol. 116, 609-622.
64. Zhang, Z., Tao, Z., Gameiro, A., Barcelona, S., Braams, S., Rauen, T., and Grewer, C. (2007) Transport direction determines the kinetics of substrate transport by the glutamate transporter EAAC1. Proc. Natl. Acad. Sci. USA 104, 18025-18030.
65. Okumoto, S., Looger, L. L., Micheva, K. D., Reimer, R. J., Smith, S. J., and Frommer, W. B. (2005) Detection of glutamate release from neurons by genetically encoded surface-displayed FRET nanosensors. Proc. Natl. Acad. Sci. USA 102, 8740-8745.
66. Grewer, C., Watzke, N., Wiessner, M., and Rauen, T. (2000) Glutamate translocation of the neuronal glutamate transporter EAAC1 occurs within milliseconds. Proc. Natl. Acad. Sci. USA 97, 9706-9711.
67. Hilgemann, D. W., and Lu, C. C. (1999) GAT1 (GABA:Na+:Cl-) cotransport function. Database reconstruction with an alternating access model. J. Gen. Physiol. 114, 459-475.
68. Lu, C. C., and Hilgemann, D. W. (1999) GAT1 (GABA:Na+:Cl-) cotransport function. Steady state studies in giant xenopus oocyte membrane patches. J. Gen. Physiol. 114, 429-444
69. Wadiche, J. I., Arriza, J. L., Amara, S. G., and Kavanaugh, M. P. (1995) Kinetics of a human glutamate transporter. Neuron 14, 1019-1027.
70. Otis, T. S., and Jahr, C. E. (1998) Anion currents and predicted glutamate flux through a neuronal glutamate transporter. J. Neurosci. 18, 7099-7110.
71. Cleland, W. W. (1963) The kinetics of enzyme-catalyzed reactions with two or more substrates or products. I. Nomenclature and rate equations. Biochim. Biophys. Acta 1000, 213-220.
72. Nicholls, D., and Attwell, D. (1990) The release and uptake of excitatory amino acids. Trends Pharmacol. Sci. 11, 462-468.
73. Dawson, L. A., Djali, S., Gonzales, C., Vinegra, M. A., and Zaleska, M. M. (2000) Characterization of transient focal ischemia-induced increases in extracellular glutamate and aspartate in spontaneously hypertensive rats. Brain Res. Bull. 53, 767-776.
74. Katayama, Y., Kawamata, T., Tamura, T., Hovda, D. A., Becker, D. P., and Tsubokawa, T. (1991) Calcium-dependent glutamate release concomitant with massive potassium flux during cerebral ischemia in vivo. Brain Res. 558, 136-140.
75. Parpura, V., Scemes, E., and Spray, D. C. (2004) Mechanisms of glutamate release from astrocytes: gap junction "hemichannels", purinergic receptors and exocytotic release. Neurochem. Int. 45, 259-264.
76. Rossi, D. J., Brady, J. D., and Mohr, C. (2007) Astrocyte metabolism and signaling during brain ischemia. Nat. Neurosci. 10, 1377-1386.
77. Rossi, D. J., Oshima, T., and Attwell, D. (2000) Glutamate release in severe brain ischaemia is mainly by reversed uptake. Nature 403, 316-321. (Pubitemid 30062388)
78. Arriza, J. L., Fairman, W. A., Wadiche, J. I., Murdoch, G. H., Kavanaugh, M. P. and Amara, S. G. (1994) Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. J. Neurosci. 14, 5559-5569.
79. Longuemare, M. C., Rose, C. R., Farrell, K., Ransom, B. R., Waxman, S. G., and Swanson, R. A. (1999) K+-induced reversal of astrocyte glutamate uptake is limited by compensatory changes in intracellular Na+. Neuroscience 93, 285-292. (Pubitemid 29290708)
80. Ottersen, O. P., Laake, J. H., Reichelt, W., Haug, F. M., and Torp, R. (1996) Ischemic disruption of glutamate homeostasis in brain: quantitative immunocytochemical analyses. J. Chem. Neuroanat. 12, 1-14.
81. Swanson, R. A. (1992) Astrocyte glutamate uptake during chemical hypoxia in vitro. Neurosci. Lett. 147, 143-146.
82. Silver, I. A., Deas, J., and Erecinska, M. (1997) Ion homeostasis in brain cells: differences in intracellular ion responses to energy limitation between cultured neurons and glial cells. Neuroscience 78, 589-601. (Pubitemid 27170347)
83. Duffy, S., and MacVicar, B. A. (1996) In vitro ischemia promotes calcium influx and intracellular calcium release in hippocampal astrocytes. J. Neurosci. 16, 71-81.
84. Brown, A. M., Baltan Tekkok, S., and Ransom, B. R. (2004) Energy transfer from astrocytes to axons: the role of CNS glycogen. Neurochem. Int. 45, 529-536.
85. Schurr, A., Payne, R. S., Miller, J. J., and Rigor, B. M. (1997) Brain lactate is an obligatory aerobic energy substrate for functional recovery after hypoxia: further in vitro validation. J. Neurochem. 69, 423-426. (Pubitemid 27274200)
86. Esslinger, C. S., Agarwal, S., Gerdes, J., Wilson, P. A., Davis, E. S., Awes, A. N., O'Brien, E., Mavencamp, T., Koch, H. P., Poulsen, D. J., Rhoderick, J. F., Chamberlin, A. R., Kavanaugh, M. P., and Bridges, R. J. (2005) The substituted aspartate analogue L-beta-threo-benzyl-aspartate preferentially inhibits the neuronal excitatory amino acid transporter EAAT3. Neuropharmacology 49, 850-861. (Pubitemid 41483891)