Excitatory amino acid transporter 3 explained

Excitatory amino acid transporter 3 (EAAT3), is a protein that in humans is encoded by the SLC1A1 gene.[1] [2]

Tissue distribution

EAAT3 is expressed on the plasma membrane of neurons, specifically on the dendrites and axon terminals.[3]

Function

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. A meta-analysis identified a small but significant association between a polymorphism of the gene SLC1A1 and Obsessive-Compulsive Disorder.[4]

Interactions

SLC1A1 has been shown to interact with ARL6IP5.[5]

See also

References

Further reading

Notes and References

  1. Smith CP, Weremowicz S, Kanai Y, Stelzner M, Morton CC, Hediger MA . 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 . March 1994 . 8020993 . 10.1006/geno.1994.1183 .
  2. Web site: Entrez Gene: SLC1A1 solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1.
  3. Underhill SM, Wheeler DS, Li M, Watts SD, Ingram SL, Amara SG . Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons . Neuron . 83 . 2 . 404–416 . July 2014 . 25033183 . 4159050 . 10.1016/j.neuron.2014.05.043 . 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. .
  4. Stewart SE, Mayerfeld C, Arnold PD, Crane JR, O'Dushlaine C, Fagerness JA, Yu D, Scharf JM, Chan E, Kassam F, Moya PR, Wendland JR, Delorme R, Richter MA, Kennedy JL, Veenstra-VanderWeele J, Samuels J, Greenberg BD, McCracken JT, Knowles JA, Fyer AJ, Rauch SL, Riddle MA, Grados MA, Bienvenu OJ, Cullen B, Wang Y, Shugart YY, Piacentini J, Rasmussen S, Nestadt G, Murphy DL, Jenike MA, Cook EH, Pauls DL, Hanna GL, Mathews CA . 6 . Meta-analysis of association between obsessive-compulsive disorder and the 3' region of neuronal glutamate transporter gene SLC1A1 . American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics . 162B . 4 . 367–79 . June 2013 . 23606572 . 10.1002/ajmg.b.32137 . 2027.42/98412 . 20929721 . free .
  5. Lin CI, Orlov I, Ruggiero AM, Dykes-Hoberg M, Lee A, Jackson M, Rothstein JD . Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18 . Nature . 410 . 6824 . 84–8 . March 2001 . 11242046 . 10.1038/35065084 . 2001Natur.410...84L . 4622513 .

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