"Diagram Illustrating the Malate-Asparate Shuttle Pathway". (Glutamate aspartate transporter labeled at bottom center.)
Expression of SLC1A3 in the Bergmann glia fibers. Mouse brain at 7th postnatal day, sagittal section; GENSAT database.
Solute carrier family 1 (glial high affinity glutamate transporter), member 3, also known as SLC1A3, is a human gene.[1]
The GLutamate ASpartate Transporter (GLAST) is a protein in the inner mitochondrial membrane which is part of the malate-aspartate shuttle.[2] GLAST is also often called the Excitatory Amino Acid Transporter 1 (EAAT1).
Mechanism
GLAST mediates the transport of glutamic and aspartic acid with the cotransport of three Na+ and one H+ cations and counter transport of one K+ cation. This co-transport coupling allows the transport of glutamate into cells against a concentration gradient.[3]
Tissue distribution
GLAST is highly expressed in astrocytes and Bergmann glia in the cerebellum.[4][5] In the retina, GLAST is expressed in Muller cells.[6] GLAST is also expressed in a number of other tissues including cardiac myocytes.[2]
Clinical significance
It is associated with type 6 episodic_ataxia.[7]
References
- ^ "Entrez Gene: SLC1A3 solute carrier family 1 (glial high affinity glutamate transporter), member 3".
- ^ a b Ralphe JC, Segar JL, Schutte BC, Scholz TD (2004). "Localization and function of the brain excitatory amino acid transporter type 1 in cardiac mitochondria". J. Mol. Cell. Cardiol. 37 (1): 33–41. doi:10.1016/j.yjmcc.2004.04.008. PMID 15242733.
- ^ Kanai Y, Hediger MA (2004). "The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects". Pflugers Arch. 447 (5): 469–79. doi:10.1007/s00424-003-1146-4. PMID 14530974.
- ^ Storck T, Schulte S, Hofmann K, Stoffel W (1992). "Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain". Proc. Natl. Acad. Sci. U.S.A. 89 (22): 10955–9. doi:10.1073/pnas.89.22.10955. PMID 1279699.
- ^ Rothstein JD, Martin L, Levey AI, Dykes-Hoberg M, Jin L, Wu D, Nash N, Kuncl RW (1994). "Localization of neuronal and glial glutamate transporters". Neuron 13 (3): 713–25. doi:10.1016/0896-6273(94)90038-8. PMID 7917301.
- ^ Rauen T, Taylor WR, Kuhlbrodt K, Wiessner M (1998). "High-affinity glutamate transporters in the rat retina: a major role of the glial glutamate transporter GLAST-1 in transmitter clearance". Cell Tissue Res. 291 (1): 19–31. doi:10.1007/s004410050976. PMID 9394040.
- ^ Jen JC, Wan J, Palos TP, Howard BD, Baloh RW (2005). "Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures". Neurology 65 (4): 529–34. doi:10.1212/01.wnl.0000172638.58172.5a. PMID 16116111.
Further reading
- Arriza JL, Fairman WA, Wadiche JI, et al. (1994). "Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex.". J. Neurosci. 14 (9): 5559–69. PMID 7521911.
- Nomura N, Nagase T, Miyajima N, et al. (1995). "Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1.". DNA Res. 1 (5): 223–9. PMID 7584044.
- Takai S, Yamada K, Kawakami H, et al. (1995). "Localization of the gene (SLC1A3) encoding human glutamate transporter (GluT-1) to 5p13 by fluorescence in situ hybridization.". Cytogenet. Cell Genet. 69 (3-4): 209–10. PMID 7698014.
- Shashidharan P, Huntley GW, Meyer T, et al. (1995). "Neuron-specific human glutamate transporter: molecular cloning, characterization and expression in human brain.". Brain Res. 662 (1-2): 245–50. PMID 7859077.
- Kirschner MA, Arriza JL, Copeland NG, et al. (1995). "The mouse and human excitatory amino acid transporter gene (EAAT1) maps to mouse chromosome 15 and a region of syntenic homology on human chromosome 5.". Genomics 22 (3): 631–3. doi:10.1006/geno.1994.1437. PMID 8001975.
- Kawakami H, Tanaka K, Nakayama T, et al. (1994). "Cloning and expression of a human glutamate transporter.". Biochem. Biophys. Res. Commun. 199 (1): 171–6. doi:10.1006/bbrc.1994.1210. PMID 8123008.
- Shashidharan P, Plaitakis A (1993). "Cloning and characterization of a glutamate transporter cDNA from human cerebellum.". Biochim. Biophys. Acta 1216 (1): 161–4. PMID 8218410.
- Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction.". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
- Stoffel W, Sasse J, Düker M, et al. (1996). "Human high affinity, Na(+)-dependent L-glutamate/L-aspartate transporter GLAST-1 (EAAT-1): gene structure and localization to chromosome 5p11-p12.". FEBS Lett. 386 (2-3): 189–93. PMID 8647279.
- Yu W, Andersson B, Worley KC, et al. (1997). "Large-scale concatenation cDNA sequencing.". Genome Res. 7 (4): 353–8. PMID 9110174.
- Dunlop J, Lou Z, McIlvain HB (1999). "Properties of excitatory amino acid transport in the human U373 astrocytoma cell line.". Brain Res. 839 (2): 235–42. PMID 10519046.
- Koch HP, Kavanaugh MP, Esslinger CS, et al. (1999). "Differentiation of substrate and nonsubstrate inhibitors of the high-affinity, sodium-dependent glutamate transporters.". Mol. Pharmacol. 56 (6): 1095–104. PMID 10570036.
- Ye ZC, Rothstein JD, Sontheimer H (2000). "Compromised glutamate transport in human glioma cells: reduction-mislocalization of sodium-dependent glutamate transporters and enhanced activity of cystine-glutamate exchange.". J. Neurosci. 19 (24): 10767–77. PMID 10594060.
- Szymocha R, Akaoka H, Dutuit M, et al. (2000). "Human T-cell lymphotropic virus type 1-infected T lymphocytes impair catabolism and uptake of glutamate by astrocytes via Tax-1 and tumor necrosis factor alpha.". J. Virol. 74 (14): 6433–41. PMID 10864655.
- Mordrelle A, Jullian E, Costa C, et al. (2000). "EAAT1 is involved in transport of L-glutamate during differentiation of the Caco-2 cell line.". Am. J. Physiol. Gastrointest. Liver Physiol. 279 (2): G366–73. PMID 10915646.
- Seal RP, Shigeri Y, Eliasof S, et al. (2002). "Sulfhydryl modification of V449C in the glutamate transporter EAAT1 abolishes substrate transport but not the substrate-gated anion conductance.". Proc. Natl. Acad. Sci. U.S.A. 98 (26): 15324–9. doi:10.1073/pnas.011400198. PMID 11752470.
- Palmada M, Kinne-Saffran E, Centelles JJ, Kinne RK (2002). "Benzodiazepines differently modulate EAAT1/GLAST and EAAT2/GLT1 glutamate transporters expressed in CHO cells.". Neurochem. Int. 40 (4): 321–6. PMID 11792462.
- Scott HL, Pow DV, Tannenberg AE, Dodd PR (2002). "Aberrant expression of the glutamate transporter excitatory amino acid transporter 1 (EAAT1) in Alzheimer's disease.". J. Neurosci. 22 (3): RC206. PMID 11826152.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.
- Vallat-Decouvelaere AV, Chrétien F, Gras G, et al. (2003). "Expression of excitatory amino acid transporter-1 in brain macrophages and microglia of HIV-infected patients. A neuroprotective role for activated microglia?". J. Neuropathol. Exp. Neurol. 62 (5): 475–85. PMID 12769187.
External links
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Membrane proteins, carrier proteins: membrane transport proteins |
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| ABC-transporter |
A1, A2, A3, A4, A7, A8, A12
B1, B2-3, B2, B3, B4, B5, B6, B7, B9, B11
C1, C2, C3, C4, C5, C6, C8, C8-9, C10, C13, C11
D1, D2, D3, D4, E1, F1, F2
G1, G2, G4, Sterolin ( G5, G8)
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| Solute carrier |
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1-10
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1A1-7, 1A1, 1A2, 1A3, 1A4, 1A5
Glucose transporter: 2A1 (GLUT1), 2A2 (GLUT2), 2A3 (GLUT3), 2A4 (GLUT4), 2A5 (GLUT5), 2A6 (SLC2A6), 2A8 (GLUT8), 2A9, 2A10, 2A12
3A1, 3A2, 4A1, 4A2, 4A3, 4A4, 4A5, 4A7, 4A8, 4A11, 5A1-2, 5A1, 5A3, 5A5, 5A8, 6A1, 6A2, 6A3, 6A4, 6A5, 6A8, 6A9, 6A19, 7A1, 7A2, 7A3, 7A4, 7A5, 7A7, 7A8, 7A9, 7A11, 8A1-3, 9A1, 9A2, 9A3, 9A3R1, 9A3R2, 9A5, 9A6, 9A8, 10A1, 10A2, 10A3, 10A7
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11-20
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11A1, 11A2, 11A3, 12A1-2, 12A3, 12A4, 12A5, 12A6, 12A7, 14A1, 13A3, 14A2, 15A1, 15A2, 16A1, 16A2, 16A3, 16A4, 17A1, 17A5, 17A6-8, 17A7, 18A1, 18A2, 18A3, 19A1, 19A2, 19A3, 20A1, 20A2
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21-30
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22A1, 22A2, 22A3, 22A4, 22A5, 22A6, 22A7, 22A9, 22A11, 22A12, 22A18, 23A1, 23A2, 24A1-2, 24A5, 25A1, 25A3, 25A4, 25A4-6, 25A8, 25A10, 25A11, 25A12, 25A13, 25A14, 25A15, 25A17, 25A19, 25A20, 25A27, 25A31, 25A37, 25A39, 26A2, 26A3, 26A4, 26A5, 26A6, 26A7, 26A8, 27A1, 27A2, 27A3, 27A4, 28A1, 28A2, 29A1, 29A2, 29A4, 30A1, 30A4, 30A7, 30A8
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31-40
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31A1, 31A2, 32A1, 34A1, 34A2, 34A3, 35A1, 35A2, 35B2, 35B4, 35C1, 36A1, 37A4, 38A2, 38A3, 39A1, 39A2, 39A3, 39A4, 39A6, 39A7
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41-45
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O
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| Other |
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Mitochondrial enzymes and transporters |
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| Outer membrane |
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| Intermembrane space |
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| Inner membrane |
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| Matrix |
citric acid cycle ( Citrate synthase, Aconitase, Isocitrate dehydrogenase, Oxoglutarate dehydrogenase, Succinyl coenzyme A synthetase, Fumarase, Malate dehydrogenase)
anaplerotic reactions (Aspartate transaminase, Glutamate dehydrogenase, Pyruvate dehydrogenase complex)
urea cycle (Carbamoyl phosphate synthetase I, Ornithine transcarbamylase, N-Acetylglutamate synthase)
alcohol metabolism ( ALDH2)
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| Other/to be sorted |
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| Mitochondrial DNA |
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