Excitatory amino acid transporter 1

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SLC1A3
Identifiers
AliasesSLC1A3, EA6, EAAT1, GLAST, GLAST1, solute carrier family 1 member 3
External IDsOMIM: 600111 MGI: 99917 HomoloGene: 20882 GeneCards: SLC1A3
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001166695
NM_001166696
NM_001289939
NM_001289940
NM_004172

NM_148938

RefSeq (protein)

NP_001160167
NP_001160168
NP_001276868
NP_001276869
NP_004163

NP_683740

Location (UCSC)Chr 5: 36.6 – 36.69 MbChr 15: 8.66 – 8.74 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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).

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]

Mechanism

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]

Tissue distribution

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]

Clinical significance

It is associated with type 6 episodic ataxia.[14] EAAT1 expression may also be associated with osteoarthritis.[15]

Pharmacology

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]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000079215 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000005360 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: SLC1A3 solute carrier family 1 (glial high affinity glutamate transporter), member 3".
  6. ^ Lehre KP, Levy LM, Ottersen OP, Storm-Mathisen J, Danbolt NC (March 1995). "Differential expression of two glial glutamate transporters in the rat brain: quantitative and immunocytochemical observations". The Journal of Neuroscience. 15 (3 Pt 1): 1835–53. doi:10.1523/JNEUROSCI.15-03-01835.1995. PMC 6578153. PMID 7891138.
  7. ^ a b Ralphe JC, Segar JL, Schutte BC, Scholz TD (July 2004). "Localization and function of the brain excitatory amino acid transporter type 1 in cardiac mitochondria". Journal of Molecular and Cellular Cardiology. 37 (1): 33–41. doi:10.1016/j.yjmcc.2004.04.008. PMID 15242733.
  8. ^ Gendreau S, Voswinkel S, Torres-Salazar D, Lang N, Heidtmann H, Detro-Dassen S, Schmalzing G, Hidalgo P, Fahlke C (September 2004). "A trimeric quaternary structure is conserved in bacterial and human glutamate transporters". The Journal of Biological Chemistry. 279 (38): 39505–12. doi:10.1074/jbc.M408038200. PMID 15265858. S2CID 16077315.
  9. ^ Kanai Y, Hediger MA (February 2004). "The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects". Pflügers Archiv. 447 (5): 469–79. doi:10.1007/s00424-003-1146-4. PMID 14530974. S2CID 21564906.
  10. ^ Danbolt NC (September 2001). "Glutamate uptake". Progress in Neurobiology. 65 (1): 1–105. doi:10.1016/S0301-0082(00)00067-8. PMID 11369436. S2CID 27347413.
  11. ^ Storck T, Schulte S, Hofmann K, Stoffel W (November 1992). "Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain". Proceedings of the National Academy of Sciences of the United States of America. 89 (22): 10955–9. Bibcode:1992PNAS...8910955S. doi:10.1073/pnas.89.22.10955. PMC 50461. PMID 1279699.
  12. ^ Rothstein JD, Martin L, Levey AI, Dykes-Hoberg M, Jin L, Wu D, Nash N, Kuncl RW (September 1994). "Localization of neuronal and glial glutamate transporters". Neuron. 13 (3): 713–25. doi:10.1016/0896-6273(94)90038-8. PMID 7917301. S2CID 45299639.
  13. ^ Rauen T, Taylor WR, Kuhlbrodt K, Wiessner M (January 1998). "High-affinity glutamate transporters in the rat retina: a major role of the glial glutamate transporter GLAST-1 in transmitter clearance". Cell and Tissue Research. 291 (1): 19–31. doi:10.1007/s004410050976. PMID 9394040. S2CID 6814592.
  14. ^ Jen JC, Wan J, Palos TP, Howard BD, Baloh RW (August 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. S2CID 22492395.
  15. ^ Mason DJ, Brakspear K, Wilson C, Williams R, Kotwal RS (July 2010). "Expression of glutamate receptors and transporters in human subchondral bone in osteoarthritis". Orthopaedic Proceedings. 93-B (SUPP_I). The British Editorial Society of Bone & Joint Surgery: 411. doi:10.1302/0301-620X.93BSUPP_I.0930069b (inactive 31 January 2024).{{cite journal}}: CS1 maint: DOI inactive as of January 2024 (link)
  16. ^ Shimamoto K, Lebrun B, Yasuda-Kamatani Y, Sakaitani M, Shigeri Y, Yumoto N, Nakajima T (February 1998). "DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters". Molecular Pharmacology. 53 (2): 195–201. doi:10.1124/mol.53.2.195. PMID 9463476.
  17. ^ Jensen AA, Erichsen MN, Nielsen CW, Stensbøl TB, Kehler J, Bunch L (February 2009). "Discovery of the first selective inhibitor of excitatory amino acid transporter subtype 1". Journal of Medicinal Chemistry. 52 (4): 912–5. doi:10.1021/jm8013458. PMID 19161278.

Further reading

External links