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Excitatory amino acid transporter 3

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 IDsMGI: 105083 HomoloGene: 20881 GeneCards: SLC1A1
Gene location (Human)
Chromosome 9 (human)
Chr.Chromosome 9 (human)[1]
Chromosome 9 (human)
Genomic location for SLC1A1
Genomic location for SLC1A1
Band9p24.2Start4,490,468 bp[1]
End4,587,469 bp[1]
RNA expression pattern
PBB GE SLC1A1 206396 at fs.png

PBB GE SLC1A1 213664 at fs.png
More reference expression data
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: 28.84 – 28.91 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Contents

Tissue distributionEdit

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

FunctionEdit

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.

InteractionsEdit

SLC1A1 has been shown to interact with ARL6IP5.[8]

See alsoEdit

ReferencesEdit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000106688 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024935 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ Smith CP, Weremowicz S, Kanai Y, Stelzner M, Morton CC, Hediger MA (August 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): 404–16. 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. ^ Lin CI, Orlov I, Ruggiero AM, Dykes-Hoberg M, Lee A, Jackson M, Rothstein JD (2001). "Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18". Nature. 410 (6824): 84–8. doi:10.1038/35065084. PMID 11242046.

Further readingEdit

  • Nieoullon A, Canolle B, Masmejean F, Guillet B, Pisano P, Lortet S (2006). "The neuronal excitatory amino acid transporter EAAC1/EAAT3: does it represent a major actor at the brain excitatory synapse?". J. Neurochem. 98 (4): 1007–18. doi:10.1111/j.1471-4159.2006.03978.x. PMID 16800850.
  • Arriza JL, Fairman WA, Wadiche JI, Murdoch GH, Kavanaugh MP, Amara SG (1994). "Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex". J. Neurosci. 14 (9): 5559–69. PMID 7521911.
  • Shashidharan P, Huntley GW, Meyer T, Morrison JH, Plaitakis A (1994). "Neuron-specific human glutamate transporter: molecular cloning, characterization and expression in human brain". Brain Res. 662 (1–2): 245–50. doi:10.1016/0006-8993(94)90819-2. PMID 7859077.
  • Kanai Y, Stelzner M, Nussberger S, Khawaja S, Hebert SC, Smith CP, Hediger MA (1994). "The neuronal and epithelial human high affinity glutamate transporter. Insights into structure and mechanism of transport". J. Biol. Chem. 269 (32): 20599–606. PMID 7914198.
  • Zerangue N, Kavanaugh MP (1996). "Interaction of L-cysteine with a human excitatory amino acid transporter". J. Physiol. 493 (Pt 2): 419–23. doi:10.1113/jphysiol.1996.sp021393. PMC 1158927. PMID 8782106.
  • Bar-Peled O, Ben-Hur H, Biegon A, Groner Y, Dewhurst S, Furuta A, Rothstein JD (1997). "Distribution of glutamate transporter subtypes during human brain development". J. Neurochem. 69 (6): 2571–80. doi:10.1046/j.1471-4159.1997.69062571.x. PMID 9375691.
  • He Y, Janssen WG, Rothstein JD, Morrison JH (2000). "Differential synaptic localization of the glutamate transporter EAAC1 and glutamate receptor subunit GluR2 in the rat hippocampus". J. Comp. Neurol. 418 (3): 255–69. doi:10.1002/(SICI)1096-9861(20000313)418:3<255::AID-CNE2>3.0.CO;2-6. PMID 10701825.
  • Lin CI, Orlov I, Ruggiero AM, Dykes-Hoberg M, Lee A, Jackson M, Rothstein JD (2001). "Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18". Nature. 410 (6824): 84–8. doi:10.1038/35065084. PMID 11242046.
  • Veenstra-VanderWeele J, Kim SJ, Gonen D, Hanna GL, Leventhal BL, Cook EH (2001). "Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder". Mol. Psychiatry. 6 (2): 160–7. doi:10.1038/sj.mp.4000806. PMID 11317217.
  • Borre L, Kavanaugh MP, Kanner BI (2002). "Dynamic equilibrium between coupled and uncoupled modes of a neuronal glutamate transporter". J. Biol. Chem. 277 (16): 13501–7. doi:10.1074/jbc.M110861200. PMID 11823462.
  • González MI, Bannerman PG, Robinson MB (2003). "Phorbol myristate acetate-dependent interaction of protein kinase Calpha and the neuronal glutamate transporter EAAC1". J. Neurosci. 23 (13): 5589–93. PMID 12843260.
  • Noorlander CW, de Graan PN, Nikkels PG, Schrama LH, Visser GH (2004). "Distribution of glutamate transporters in the human placenta". Placenta. 25 (6): 489–95. doi:10.1016/j.placenta.2003.10.018. PMID 15135231.
  • Koch HP, Larsson HP (2005). "Small-scale molecular motions accomplish glutamate uptake in human glutamate transporters". J. Neurosci. 25 (7): 1730–6. doi:10.1523/JNEUROSCI.4138-04.2005. PMID 15716409.
  • Vallejo-Illarramendi A, Domercq M, Pérez-Cerdá F, Ravid R, Matute C (2006). "Increased expression and function of glutamate transporters in multiple sclerosis". Neurobiol. Dis. 21 (1): 154–64. doi:10.1016/j.nbd.2005.06.017. PMID 16061389.
  • Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
  • Rainesalo S, Keränen T, Saransaari P, Honkaniemi J (2005). "GABA and glutamate transporters are expressed in human platelets". Brain Res. Mol. Brain Res. 141 (2): 161–5. doi:10.1016/j.molbrainres.2005.08.013. PMID 16198020.

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