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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.[2] 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.
↑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. PMID8020993.
↑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. PMID11242046.
Further reading
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. PMID16800850.
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. PMID7521911.
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. PMID7859077.
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. PMID7914198.
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. PMID9375691.
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. PMID11242046.
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. PMID11317217.
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. PMID11823462.
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. PMID12843260.
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. PMID15135231.
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. PMID15716409.
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. PMID16061389.
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. PMID16189514.
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. PMID16198020.