Glutamate aspartate transporter

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"Diagram Illustrating the Malate-Asparate Shuttle Pathway". (Glutamate aspartate transporter labeled at bottom center.)
"Diagram Illustrating the Malate-Asparate Shuttle Pathway". (Glutamate aspartate transporter labeled at bottom center.)


Solute carrier family 1 (glial high affinity glutamate transporter), member 3
Identifiers
Symbol(s) SLC1A3; EA6; EAAT1; FLJ25094; GLAST; GLAST1
External IDs OMIM: 600111 MGI: 99917 HomoloGene: 20882
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 6507 20512
Ensembl ENSG00000079215 ENSMUSG00000005360
Uniprot P43003 Q543U3
Refseq NM_004172 (mRNA)
NP_004163 (protein)		 NM_148938 (mRNA)
NP_683740 (protein)
Location Chr 5: 36.64 - 36.72 Mb Chr 15: 8.58 - 8.66 Mb
Pubmed search [1] [2]

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).

Contents

[edit] 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]

[edit] 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]

[edit] Clinical significance

It is associated with type 6 episodic_ataxia.[7]

[edit] References

  1. ^ Entrez Gene: SLC1A3 solute carrier family 1 (glial high affinity glutamate transporter), member 3.
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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. 

[edit] 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. 

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Complex I (7 units) - Complex III (1 unit) - Complex IV (3 units) - ATP synthase (2 units)