Excitatory amino acid transporter 3 is a member of the high-affinityglutamate transporters which plays an essential role in transportingglutamate acrossplasma membranes inneurons. In the brain, excitatory amino acid transporters are crucial in terminating the postsynaptic action of theneurotransmitter glutamate, and in maintaining extracellular glutamate concentrations below neurotoxic levels. EAAT3 also transportsaspartate, and mutations in this gene are thought to causedicarboxylic 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 andObsessive-Compulsive Disorder.[8]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^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.PMID8020993.
^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.PMC4159050.PMID25033183.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.
^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.PMID11242046.S2CID4622513.
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.PMID11242046.S2CID4622513.
Veenstra-VanderWeele J, Kim SJ, Gonen D, Hanna GL, Leventhal BL, Cook EH (March 2001). "Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder".Molecular Psychiatry.6 (2):160–7.doi:10.1038/sj.mp.4000806.PMID11317217.S2CID13969870.
Noorlander CW, de Graan PN, Nikkels PG, Schrama LH, Visser GH (July 2004). "Distribution of glutamate transporters in the human placenta".Placenta.25 (6):489–95.doi:10.1016/j.placenta.2003.10.018.PMID15135231.
Vallejo-Illarramendi A, Domercq M, Pérez-Cerdá F, Ravid R, Matute C (January 2006). "Increased expression and function of glutamate transporters in multiple sclerosis".Neurobiology of Disease.21 (1):154–64.doi:10.1016/j.nbd.2005.06.017.PMID16061389.S2CID17817187.
