Glutamate aspartate transporter

SLC1A3
Identifiers
Aliases SLC1A3, EA6, EAAT1, GLAST, GLAST1, solute carrier family 1 member 3
External IDs OMIM: 600111 MGI: 99917 HomoloGene: 20882 GeneCards: SLC1A3
Targeted by Drug
DL-TBOA[1]
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez

6507

20512

Ensembl

ENSG00000079215

ENSMUSG00000005360

UniProt

P43003

P56564

RefSeq (mRNA)

NM_001166695
NM_001166696
NM_001289939
NM_001289940
NM_004172

NM_148938

RefSeq (protein)

NP_001160167.1
NP_001276869.1
NP_004163.3

NP_683740.1

Location (UCSC) Chr 5: 36.61 – 36.69 Mb Chr 15: 8.63 – 8.71 Mb
PubMed search [2] [3]
Wikidata
View/Edit HumanView/Edit Mouse

Solute carrier family 1 (glial high-affinity glutamate transporter), member 3, also known as SLC1A3, is a protein that, in humans, is encoded by the SLC1A3 gene.[4] SLC1A3 is also often called the GLutamate ASpartate Transporter (GLAST) or Excitatory Amino Acid Transporter 1 (EAAT1) .

GLAST is predominantly expressed in the plasma membrane, allowing it to remove glutamate from the extracellular space.[5] It has also been localized in the inner mitochondrial membrane as part of the malate-aspartate shuttle.[6]

Mechanism

GLAST functions in vivo as a homotrimer.[7] 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 (or symport) allows the transport of glutamate into cells against a concentration gradient.[8]

"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. 

Tissue distribution

GLAST is expressed throughout the CNS,[9] and is highly expressed in astrocytes and Bergmann glia in the cerebellum.[10][11] In the retina, GLAST is expressed in Muller cells.[12] GLAST is also expressed in a number of other tissues including cardiac myocytes.[6]

Clinical significance

It is associated with type 6 episodic_ataxia.[13]

Pharmacology

DL-threo-beta-benzyloxyaspartate (TBOA) is an inhibitor of the excitatory amino acid transporters.[14]

Selective inhibitors for GLAST 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.[15]

References

  1. ↑ "Drugs that physically interact with Excitatory amino acid transporter 1 view/edit references on wikidata".
  2. ↑ "Human PubMed Reference:".
  3. ↑ "Mouse PubMed Reference:".
  4. ↑ "Entrez Gene: SLC1A3 solute carrier family 1 (glial high affinity glutamate transporter), member 3".
  5. ↑ 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 : the official journal of the Society for Neuroscience. 15 (3 Pt 1): 1835–53. PMID 7891138.
  6. 1 2 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.
  7. ↑ Gendreau S, Voswinkel S, Torres-Salazar D, Lang N, Heidtmann H, Detro-Dassen S, Schmalzing G, Hidalgo P, Fahlke C (Sep 17, 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.
  8. ↑ 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.
  9. ↑ Danbolt NC (September 2001). "Glutamate uptake". Prog. Neurobiol. 65 (1): 1–105. doi:10.1016/S0301-0082(00)00067-8. PMID 11369436.
  10. ↑ 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. PMC 50461Freely accessible. PMID 1279699.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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. PMID 9463476.
  15. ↑ Jensen AA, Erichsen MN, Nielsen CW, Stensbøl TB, Kehler J, Bunch L (Feb 26, 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

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