Glutamate aspartate transporter

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Solute carrier family 1 (glial high affinity glutamate transporter), member 3
Identifiers
Symbols SLC1A3 ; EA6; EAAT1; GLAST; GLAST1
External IDs OMIM600111 MGI99917 HomoloGene20882 ChEMBL: 3085 GeneCards: SLC1A3 Gene
RNA expression pattern
PBB GE SLC1A3 202800 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 6507 20512
Ensembl ENSG00000079215 ENSMUSG00000005360
UniProt P43003 P56564
RefSeq (mRNA) NM_001166695 NM_148938
RefSeq (protein) NP_001160167 NP_683740
Location (UCSC) Chr 5:
36.61 – 36.69 Mb
Chr 15:
8.63 – 8.71 Mb
PubMed search [1] [2]

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.[1] 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.[2] It has also been localized in the inner mitochondrial membrane as part of the malate-aspartate shuttle.[3]

Mechanism[edit]

GLAST functions in vivo as a homotrimer.[4] 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.[5]

"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[edit]

GLAST is expressed throughout the CNS,[6] and is highly expressed in astrocytes and Bergmann glia in the cerebellum.[7][8] In the retina, GLAST is expressed in Muller cells.[9] GLAST is also expressed in a number of other tissues including cardiac myocytes.[3]

Clinical significance[edit]

It is associated with type 6 episodic_ataxia.[10]

Pharmacology[edit]

DL-threo-beta-benzyloxyaspartate (TBOA) is an inhibitor of the excitatory amino acid transporters.[11]

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.[12]

References[edit]

  1. ^ "Entrez Gene: SLC1A3 solute carrier family 1 (glial high affinity glutamate transporter), member 3". 
  2. ^ 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. 
  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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ Danbolt NC (September 2001). "Glutamate uptake". Prog. Neurobiol. 65 (1): 1–105. doi:10.1016/S0301-0082(00)00067-8. PMID 11369436. 
  7. ^ 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 50461. PMID 1279699. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ 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 Medical Chemistry 52 (4): 912–5. doi:10.1021/jm8013458. PMID 19161278. 

Further reading[edit]

External links[edit]