Excitatory amino acid transporter 1 (EAAT1) is a protein that, in humans, is encoded by the SLC1A3 gene.[5] EAAT1 is also often called the GLutamate ASpartate Transporter 1 (GLAST-1).
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EAAT1 is predominantly expressed in the plasma membrane, allowing it to remove glutamate from the extracellular space.[6] It has also been localized in the inner mitochondrial membrane as part of the malate-aspartate shuttle.[7]
EAAT1 functions in vivo as a homotrimer.[8] EAAT1 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 (or symport) allows the transport of glutamate into cells against a concentration gradient.[9]
"Diagram Illustrating the Malate-Aspartate 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.
EAAT1 is expressed throughout the CNS,[10] and is highly expressed in astrocytes and Bergmann glia in the cerebellum.[11][12] In the retina, EAAT1 is expressed in Muller cells.[13] EAAT1 is also expressed in a number of other tissues including cardiac myocytes.[7]
It is associated with type 6 episodic ataxia.[14] EAAT1 expression may also be associated with osteoarthritis.[15]
DL-threo-beta-benzyloxyaspartate (TBOA) is an inhibitor of the excitatory amino acid transporters.[16]
Selective inhibitors for EAAT1 have recently been discovered based on 25 combinations of substitutions at the 4 and 7 positions of 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitril.[17]
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- Stoffel W, Sasse J, Düker M, Müller R, Hofmann K, Fink T, Lichter P (May 1996). "Human high affinity, Na(+)-dependent L-glutamate/L-aspartate transporter GLAST-1 (EAAT-1): gene structure and localization to chromosome 5p11-p12". FEBS Letters. 386 (2–3): 189–93. doi:10.1016/0014-5793(96)00424-3. PMID 8647279. S2CID 890022.
- Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (April 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
- Dunlop J, Lou Z, McIlvain HB (August 1999). "Properties of excitatory amino acid transport in the human U373 astrocytoma cell line". Brain Research. 839 (2): 235–42. doi:10.1016/S0006-8993(99)01714-X. PMID 10519046. S2CID 7021891.
- Koch HP, Kavanaugh MP, Esslinger CS, Zerangue N, Humphrey JM, Amara SG, Chamberlin AR, Bridges RJ (December 1999). "Differentiation of substrate and nonsubstrate inhibitors of the high-affinity, sodium-dependent glutamate transporters". Molecular Pharmacology. 56 (6): 1095–104. doi:10.1124/mol.56.6.1095. PMID 10570036.
- Ye ZC, Rothstein JD, Sontheimer H (December 1999). "Compromised glutamate transport in human glioma cells: reduction-mislocalization of sodium-dependent glutamate transporters and enhanced activity of cystine-glutamate exchange". The Journal of Neuroscience. 19 (24): 10767–77. doi:10.1523/jneurosci.19-24-10767.1999. PMC 6784962. PMID 10594060.
- Szymocha R, Akaoka H, Dutuit M, Malcus C, Didier-Bazes M, Belin MF, Giraudon P (July 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". Journal of Virology. 74 (14): 6433–41. doi:10.1128/JVI.74.14.6433-6441.2000. PMC 112151. PMID 10864655.
- Mordrelle A, Jullian E, Costa C, Cormet-Boyaka E, Benamouzig R, Tomé D, Huneau JF (August 2000). "EAAT1 is involved in transport of L-glutamate during differentiation of the Caco-2 cell line". American Journal of Physiology. Gastrointestinal and Liver Physiology. 279 (2): G366-73. doi:10.1152/ajpgi.2000.279.2.G366. PMID 10915646. S2CID 45577626.
- Seal RP, Shigeri Y, Eliasof S, Leighton BH, Amara SG (December 2001). "Sulfhydryl modification of V449C in the glutamate transporter EAAT1 abolishes substrate transport but not the substrate-gated anion conductance". Proceedings of the National Academy of Sciences of the United States of America. 98 (26): 15324–9. Bibcode:2001PNAS...9815324S. doi:10.1073/pnas.011400198. PMC 65028. PMID 11752470.
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- Vallat-Decouvelaere AV, Chrétien F, Gras G, Le Pavec G, Dormont D, Gray F (May 2003). "Expression of excitatory amino acid transporter-1 in brain macrophages and microglia of HIV-infected patients. A neuroprotective role for activated microglia?". Journal of Neuropathology and Experimental Neurology. 62 (5): 475–85. doi:10.1093/jnen/62.5.475. PMID 12769187. S2CID 11183438.