Excitatory amino acid transporter 3

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Excitatory amino acid transporter 3 (EAAT3), is a protein that in humans is encoded by the SLC1A1 gene.[5][6]

SLC1A1
Identifiers
AliasesSLC1A1, EAAC1, EAAT3, SCZD18, DCBXA, solute carrier family 1 member 1
External IDsOMIM: 133550; MGI: 105083; HomoloGene: 20881; GeneCards: SLC1A1; OMA:SLC1A1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004170

NM_009199

RefSeq (protein)

NP_004161

NP_033225

Location (UCSC)Chr 9: 4.49 – 4.59 MbChr 19: 28.81 – 28.89 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Tissue distribution

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EAAT3 is expressed on the plasma membrane of neurons, specifically on the dendrites and axon terminals.[7]

Function

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Excitatory amino acid transporter 3 is a member of the high-affinity glutamate transporters which plays an essential role in transporting glutamate across plasma membranes in neurons. In the brain, excitatory amino acid transporters are crucial in terminating the postsynaptic action of the neurotransmitter glutamate, and in maintaining extracellular glutamate concentrations below neurotoxic levels. EAAT3 also transports aspartate, and mutations in this gene are thought to cause dicarboxylic aminoaciduria, also known as glutamate-aspartate transport defect.[6] EAAT3 is also the major route of neuronal cysteine uptake. Cysteine is a component of the major antioxidant glutathione, and mice lacking EAAT3 exhibit reduced levels of glutathione in neurons, increased oxidative stress, and age-dependent loss of neurons, especially neurons of the substantia nigra. A meta-analysis identified a small but significant association between a polymorphism of the gene SLC1A1 and Obsessive-Compulsive Disorder.[8]

Interactions

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SLC1A1 has been shown to interact with ARL6IP5.[9]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000106688Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024935Ensembl, 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. ^ Smith CP, Weremowicz S, Kanai Y, Stelzner M, Morton CC, Hediger MA (March 1994). "Assignment of the gene coding for the human high-affinity glutamate transporter EAAC1 to 9p24: potential role in dicarboxylic aminoaciduria and neurodegenerative disorders". Genomics. 20 (2): 335–6. doi:10.1006/geno.1994.1183. PMID 8020993.
  6. ^ a b "Entrez Gene: SLC1A1 solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1".
  7. ^ Underhill SM, Wheeler DS, Li M, Watts SD, Ingram SL, Amara SG (July 2014). "Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons". Neuron. 83 (2): 404–416. doi:10.1016/j.neuron.2014.05.043. PMC 4159050. PMID 25033183. In general, EAATs 1 and 2 are found predominantly in astrocytes, EAAT3 in neurons, EAAT4 in Purkinje cells, and EAAT5 expression is restricted to the retina (Danbolt, 2001). The dependence of EAAT3 internalization on the DAT also suggests that the two transporters might be internalized together. We found that EAAT3 and DAT are expressed in the same cells, as well as in axons and dendrites. However, the subcellular co-localization of the two neurotransmitter transporters remains to be established definitively by high resolution electron microscopy.
  8. ^ Stewart SE, Mayerfeld C, Arnold PD, Crane JR, O'Dushlaine C, Fagerness JA, et al. (June 2013). "Meta-analysis of association between obsessive-compulsive disorder and the 3' region of neuronal glutamate transporter gene SLC1A1" (PDF). American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 162B (4): 367–79. doi:10.1002/ajmg.b.32137. hdl:2027.42/98412. PMID 23606572. S2CID 20929721.
  9. ^ Lin CI, Orlov I, Ruggiero AM, Dykes-Hoberg M, Lee A, Jackson M, Rothstein JD (March 2001). "Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18". Nature. 410 (6824): 84–8. Bibcode:2001Natur.410...84L. doi:10.1038/35065084. PMID 11242046. S2CID 4622513.

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.