The GLT-1 (EAAT2; Slc1a2) glutamate transporter is essential for glutamate homeostasis in the neocortex of the mouse

Journal of Neurochemistry

Volumn 128, Issue 5, 2014, Pages 641-649

  Bjørnsen, Lars Petter ^a   Hadera, Mussie G ^b   Zhou, Yun ^a   Danbolt, Niels C ^a   Sonnewald, Ursula ^b  

^a UNIVERSITY OF OSLO   (Norway)

^b NORWEGIAN UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Norway)

Author keywords

GLT 1 knockout; Glutamate metabolism; Glutamate uptake; Neocortex; Neurotransmitter transport; NMR spectroscopy

Indexed keywords

CARBON 13; EXCITATORY AMINO ACID TRANSPORTER 2; GLUTAMIC ACID;

AMINO ACID METABOLISM; AMINO ACID TRANSPORT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; ASTROCYTE; CARBOXYLATION; CEREBELLUM; CONTROLLED STUDY; FEMALE; FRONTAL CORTEX; INTRACELLULAR SPACE; ISOTOPE LABELING; KNOCKOUT MOUSE; MALE; METABOLITE; MITOCHONDRIAL RESPIRATION; MOUSE; NEOCORTEX; NERVE ENDING; NEUROTRANSMISSION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; WILD TYPE;

MUS;

GLT-1 KNOCKOUT; GLUTAMATE METABOLISM; GLUTAMATE UPTAKE; NEOCORTEX; NEUROTRANSMITTER TRANSPORT; NMR SPECTROSCOPY;

AMINO ACIDS; ANIMALS; CEREBELLUM; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DATA INTERPRETATION, STATISTICAL; ENERGY METABOLISM; EXCITATORY AMINO ACID TRANSPORTER 2; FEMALE; GLUCOSE; GLUTAMIC ACID; HOMEOSTASIS; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MICE; MICE, KNOCKOUT; NEOCORTEX; PYRUVIC ACID;

EID: 84896725751     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/jnc.12509     Document Type: Article

References (58)

1. Beart P. M., and, O'Shea R. D., (2007) Transporters for L-glutamate: an update on their molecular pharmacology and pathological involvement. Br. J. Pharmacol. 150, 5-17.
2. Bjørås M., Gjesdal O., Erickson J. D., Torp R., Levy L. M., Ottersen O. P., Degree M., StormMathisen J., Seeberg E., and, Danbolt N. C., (1996) Cloning and expression of a neuronal rat brain glutamate transporter. Brain Res. Mol. Brain Res. 36, 163-168.
3. Chaudhry F. A., Reimer R. J., and, Edwards R. H., (2002) The glutamine commute: take the N line and transfer to the A. J. Cell Biol. 157, 349-355.
4. Chen W., Mahadomrongkul V., Berger U. V., Bassan M., DeSilva T., Tanaka K., Irwin N., Aoki C., and, Rosenberg P. A., (2004) The glutamate transporter GLT1a is expressed in excitatory axon terminals of mature hippocampal neurons. J. Neurosci. 24, 1136-1148.
5. Conti F., and, Melone M., (2006) The glutamine commute: lost in the tube? Neurochem. Int. 48, 459-464.
6. Danbolt N. C., (2001) Glutamate uptake. Prog. Neurobiol. 65, 1-105.
7. Danbolt N. C., Storm-Mathisen J., and, Kanner B. I., (1992) An [Na+ + K+]coupled L-glutamate transporter purified from rat brain is located in glial cell processes. Neuroscience 51, 295-310.
8. Diamond J. S., (2005) Deriving the glutamate clearance time course from transporter currents in CA1 hippocampal astrocytes: transmitter uptake gets faster during development. J. Neurosci. 25, 2906-2916.
9. Fonnum F., (1984) Glutamate: a neurotransmitter in mammalian brain. J. Neurochem. 42, 1-11.
10. Furness D. N., Dehnes Y., Akhtar A. Q., et al,. (2008) 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 157, 80-94.
11. Geddes J. W., and, Wood J. D., (1984) Changes in the amino acid content of nerve endings (synaptosomes) induced by drugs that alter the metabolism of glutamate and gamma-aminobutyric acid. J. Neurochem. 42, 16-24.
12. 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. Membrane Biol. 203, 1-20.
13. Gundersen V., Danbolt N. C., Ottersen O. P., and, Storm-Mathisen J., (1993) Demonstration of glutamate/aspartate uptake activity in nerve endings by use of antibodies recognizing exogenous D-aspartate. Neuroscience 57, 97-111.
14. Hassel B., Sonnewald U., and, Fonnum F., (1995) Glial-neuronal interactions as studied by cerebral metabolism of [2-13C]acetate and [1-13C]glucose: an ex vivo 13C NMR spectroscopic study. J. Neurochem. 64, 2773-2782.
15. Hassel B., Bachelard H., Jones P., Fonnum F., and, Sonnewald U., (1997) Trafficking of amino acids between neurons and glia in vivo. Effects of inhibition of glial metabolism by fluoroacetate. J. Cereb. Blood Flow Metab. 17, 1230-1238.
16. Haugeto O., Ullensvang K., Levy L. M., Chaudhry F. A., Honore T., Nielsen M., Lehre K. P., and, Danbolt N. C., (1996) Brain glutamate transporter proteins form homomultimers. J. Biol. Chem. 271, 27715-27722.
17. Hertz L., Yu A., Svenneby G., Kvamme E., Fosmark H., and, Schousboe A., (1980) Absence of preferential glutamine uptake into neurons-an indication of a net transfer of TCA constituents from nerve endings to astrocytes? Neurosci. Lett. 16, 103-109.
18. Holmseth S., Scott H. A., Real K., Lehre K. P., Leergaard T. B., Bjaalie J. G., and, Danbolt N. C., (2009) 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 162, 1055-1071.
19. Holmseth S., Dehnes Y., Huang Y. H., et al,. (2012) The density of EAAC1 (EAAT3) glutamate transporters expressed by neurons in the mammalian CNS. J. Neurosci. 32, 6000-6013.
20. Jenstad M., Quazi A. Z., Zilberter M., et al,. (2009) System A transporter SAT2 mediates replenishment of dendritic glutamate pools controlling retrograde signaling by glutamate. Cereb. Cortex 19, 1092-1106.
21. Johnston G. A., (1981) Glutamate uptake and its possible role in neurotransmitter inactivation, in Glutamate: Transmitter in the Central Nervous System, (P, (, Roberts J., Storm-Mathisen J., and, Johnston G. A., eds), John Wiley & Sons, Chichester, New York, Brisbane, Toronto.
22. Kanai Y., and, Hediger M. A., (1992) Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 360, 467-471.
23. Kiryk A., Aida T., Tanaka K., Banerjee P., Wilczynski G. M., Meyza K., Knapska E., Filipkowski R. K., Kaczmarek L., and, Danysz W., (2008) Behavioral characterization of GLT1 (+/-) mice as a model of mild glutamatergic hyperfunction. Neurotox. Res. 13, 19-30.
24. Le Belle J. E., Harris N. G., Williams S. R., and, Bhakoo K. K., (2002) A comparison of cell and tissue extraction techniques using high-resolution 1H-NMR spectroscopy. NMR Biomed. 15, 37-44.
25. Lehre K. P., and, Danbolt N. C., (1998) The number of glutamate transporter subtype molecules at glutamatergic synapses: chemical and stereological quantification in young adult rat brain. J. Neurosci. 18, 8751-8757.
26. Lehre K. P., Levy L. M., Ottersen O. P., Storm-Mathisen J., and, Danbolt N. C., (1995) Differential expression of two glial glutamate transporters in the rat brain: quantitative and immunocytochemical observations. J. Neurosci. 15, 1835-1853.
27. Lehre A. C., Rowley N. M., Zhou Y., et al,. (2011) Deletion of the betaine-GABA transporter (BGT1; slc6a12) gene does not affect seizure thresholds of adult mice. Epilepsy Res. 95, 70-81.
28. Levy L. M., Lehre K. P., Rolstad B., and, Danbolt N. C., (1993) A monoclonal antibody raised against an [Na(+)+K+]coupled L-glutamate transporter purified from rat brain confirms glial cell localization. FEBS Lett. 317, 79-84.
29. Logan W. J., and, Snyder S. H., (1971) Unique high affinity uptake systems for glycine, glutamic and aspartic acids in central nervous tissue of the rat. Nature 234, 297-299.
30. Mackenzie B., and, Erickson J. D., (2004) Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family. Pflugers Arch. 447, 784-795.
31. Martinez-Hernandez A., Bell K. P., and, Norenberg M. D., (1977) Glutamine synthetase: glial localization in brain. Science 195, 1356-1358.
32. Matsugami T. R., Tanemura K., Mieda M., et al,. (2006) From the Cover: indispensability of the glutamate transporters GLAST and GLT1 to brain development. Proc. Natl Acad. Sci. USA 103, 12161-12166.
33. McMahon H. T., and, Nicholls D. G., (1990) Glutamine and aspartate loading of synaptosomes: a reevaluation of effects on calcium-dependent excitatory amino acid release. J. Neurochem. 54, 373-380.
34. Melo T. M., Nehlig A., and, Sonnewald U., (2005) Metabolism is normal in astrocytes in chronically epileptic rats: a (13)C NMR study of neuronal-glial interactions in a model of temporal lobe epilepsy. J. Cereb. Blood Flow Metab. 25, 1254-1264.
35. Melone M., Bellesi M., Ducati A., Iacoangeli M., and, Conti F., (2011) Cellular and Synaptic Localization of EAAT2a in Human Cerebral Cortex. Front. Neuroanat. 4, 151.
36. 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.
37. 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.
38. Patel M. S., (1974) The relative significance of CO2-fixing enzymes in the metabolism of rat brain. J. Neurochem. 22, 717-724.
39. 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.
40. Qu H., Haberg A., Haraldseth O., Unsgard G., and, Sonnewald U., (2000) (13)C MR spectroscopy study of lactate as substrate for rat brain. Dev. Neurosci. 22, 429-436.
41. Qu H., Eloqayli H., Unsgard G., and, Sonnewald U., (2001) Glutamate decreases pyruvate carboxylase activity and spares glucose as energy substrate in cultured cerebellar astrocytes. J. Neurosci. Res. 66, 1127-1132.
42. Shank R. P., Bennett G. S., Freytag S. O., and, Campbell G. L., (1985) Pyruvate carboxylase: an astrocyte-specific enzyme implicated in the replenishment of amino acid neurotransmitter pools. Brain Res. 329, 364-367.
43. Shashidharan P., Huntley G. W., Murray J. M., Buku A., Moran T., Walsh M. J., Morrison J. H., and, Plaitakis A., (1997) Immunohistochemical localization of the neuron-specific glutamate transporter EAAC1 (EAAT3) in rat brain and spinal cord revealed by a novel monoclonal antibody. Brain Res. 773, 139-148.
44. Sibson N. R., Mason G. F., Shen J., Cline G. W., Herskovits A. Z., Wall J. E., Behar K. L., Rothman D. L., and, Shulman R. G., (2001) In vivo (13)C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during. J. Neurochem. 76, 975-989.
45. Solbu T. T., Bjorkmo M., Berghuis P., Harkany T., and, Chaudhry F. A., (2010) SAT1, A Glutamine Transporter, is Preferentially Expressed in GABAergic Neurons. Front. Neuroanat. 4, 1.
46. Sonnewald U., Westergaard N., Schousboe A., Svendsen J. S., Unsgard G., and, Petersen S. B., (1993) Direct demonstration by [13C]NMR spectroscopy that glutamine from astrocytes is a precursor for GABA synthesis in neurons. Neurochem. Int. 22, 19-29.
47. 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.
48. Storm-Mathisen J., Danbolt N. C., Rothe F., Torp R., Zhang N., Aas J. E., Kanner B. I., Langmoen I., and, Ottersen O. P., (1992) Ultrastructural immunocytochemical observations on the localization, metabolism and transport of glutamate in normal and ischemic brain tissue. Prog. Brain Res. 94, 225-241.
49. Sun Y., Petr G. T., Frederick N. M., Aoki C. J., Rotenberg A., Dhamne S. C., Hameed M. Q., Goodrich G. S., Armsen W., and, Rosenberg P. A., (2013) Glutamate uptake into mouse forebrain synaptosomes is primarily mediated by GLT-1 expressed in neurons. Soc Neurosci Abstracts 131.05.
50. Takatsuru Y., Iino M., Tanaka K., and, Ozawa S., (2007) Contribution of glutamate transporter GLT-1 to removal of synaptically released glutamate at climbing fiber-Purkinje cell synapses. Neurosci. Lett. 420, 85-89.
51. Tanaka K., Watase K., Manabe T., et al,. (1997) Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science 276, 1699-1702.
52. Tzingounis A. V., and, Wadiche J. I., (2007) Glutamate transporters: confining runaway excitation by shaping synaptic transmission. Nat. Rev. Neurosci. 8, 935-947.
53. Ullensvang K., Lehre K. P., Storm-Mathisen J., and, Danbolt N. C., (1997) Differential developmental expression of the two rat brain glutamate transporter proteins GLAST and GLT. Eur. J. Neurosci. 9, 1646-1655.
54. Voutsinos-Porche B., Bonvento G., Tanaka K., Steiner P., Welker E., Chatton J. Y., Magistretti P. J., and, Pellerin L., (2003) Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex. Neuron 37, 275-286.
55. Waniewski R. A., and, Martin D. L., (1998) Preferential utilization of acetate by astrocytes is attributable to transport. J. Neurosci. 18, 5225-5233.
56. Wilkin G. P., Garthwaite J., and, Balazs R., (1982) Putative acidic amino acid transmitters in the cerebellum. II. Electron microscopic localization of transport sites. Brain Res. 244, 69-80.
57. Yu A. C., and, Hertz L., (1982) Uptake of glutamate, GABA, and glutamine into a predominantly GABA-ergic and a predominantly glutamatergic nerve cell population in culture. J. Neurosci. Res. 7, 23-35.
58. Zhou Y., Wang X. Y., Tzingounis A. V., Danbolt N. C., and, Larsson H. P., (2013) Modeling of glutamate transporters reconstituted in liposomes argues against heteroexchange being substantially faster than net uptake. Soc Neurosci Abstracts 703.05.