View source for Biology:Excitatory amino acid transporter 3

{{Short description|Protein found in humans}}
{{Infobox_gene}}
'''Excitatory amino acid transporter 3''' ('''EAAT3'''), is a [[Biology:Protein|protein]] that in humans is encoded by the ''SLC1A1'' [[Biology:Gene|gene]].<ref name="pmid8020993">{{cite journal | vauthors = Smith CP, Weremowicz S, Kanai Y, Stelzner M, Morton CC, Hediger MA | title = Assignment of the gene coding for the human high-affinity glutamate transporter EAAC1 to 9p24: potential role in dicarboxylic aminoaciduria and neurodegenerative disorders | journal = Genomics | volume = 20 | issue = 2 | pages = 335–6 | date = March 1994 | pmid = 8020993 | doi = 10.1006/geno.1994.1183 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SLC1A1 solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6505 }}</ref>

==Tissue distribution==
EAAT3 is expressed on the [[Biology:Plasma membrane|plasma membrane]] of neurons, specifically on the dendrites and [[Biology:Axon terminal|axon terminal]]s.<ref name="EAAT3">{{cite journal | vauthors = Underhill SM, Wheeler DS, Li M, Watts SD, Ingram SL, Amara SG | title = Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons | journal = Neuron | volume = 83 | issue = 2 | pages = 404–416 | date = July 2014 | pmid = 25033183 | pmc = 4159050 | doi = 10.1016/j.neuron.2014.05.043 | quote = 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).&nbsp;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. }}</ref>

== Function ==

Excitatory amino acid transporter 3 is a member of the high-affinity [[Biology:Glutamate transporter|glutamate transporter]]s which plays an essential role in transporting glutamate across [[Biology:Plasma membrane|plasma membrane]]s in [[Biology:Neuron|neuron]]s. In the brain, excitatory amino acid transporters are crucial in terminating the postsynaptic action of the [[Biology:Neurotransmitter|neurotransmitter]] glutamate, and in maintaining extracellular glutamate concentrations below neurotoxic levels. EAAT3 also transports aspartate, and mutations in this gene are thought to cause [[Medicine:Dicarboxylic aminoaciduria|dicarboxylic aminoaciduria]], also known as glutamate-aspartate transport defect.<ref name="entrez"/>  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.<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Meta-analysis of association between obsessive-compulsive disorder and the 3' region of neuronal glutamate transporter gene SLC1A1 | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 162B | issue = 4 | pages = 367–79 | date = June 2013 | pmid = 23606572 | doi = 10.1002/ajmg.b.32137 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/98412/1/32137_ftp.pdf | hdl = 2027.42/98412 | s2cid = 20929721 | hdl-access = free }}</ref>

== Interactions ==

SLC1A1 has been shown to interact with ARL6IP5.<ref name="pmid11242046">{{cite journal | vauthors = Lin CI, Orlov I, Ruggiero AM, Dykes-Hoberg M, Lee A, Jackson M, Rothstein JD | title = Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18 | journal = Nature | volume = 410 | issue = 6824 | pages = 84–8 | date = March 2001 | pmid = 11242046 | doi = 10.1038/35065084 | bibcode = 2001Natur.410...84L | s2cid = 4622513 }}</ref>

== See also ==
* Excitatory amino acid transporter
* [[Biology:Glutamate transporter|Glutamate transporter]]
* [[Biology:Solute carrier family|Solute carrier family]]

== References ==
{{Reflist}}
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== Further reading ==
{{Refbegin | 2}}
* {{cite journal | vauthors = Nieoullon A, Canolle B, Masmejean F, Guillet B, Pisano P, Lortet S | title = The neuronal excitatory amino acid transporter EAAC1/EAAT3: does it represent a major actor at the brain excitatory synapse? | journal = Journal of Neurochemistry | volume = 98 | issue = 4 | pages = 1007–18 | date = August 2006 | pmid = 16800850 | doi = 10.1111/j.1471-4159.2006.03978.x | s2cid = 22532007 | doi-access = free }}
* {{cite journal | vauthors = Arriza JL, Fairman WA, Wadiche JI, Murdoch GH, Kavanaugh MP, Amara SG | title = Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex | journal = The Journal of Neuroscience | volume = 14 | issue = 9 | pages = 5559–69 | date = September 1994 | pmid = 7521911 | pmc = 6577102 | doi =  10.1523/jneurosci.14-09-05559.1994}}
* {{cite journal | vauthors = Shashidharan P, Huntley GW, Meyer T, Morrison JH, Plaitakis A | title = Neuron-specific human glutamate transporter: molecular cloning, characterization and expression in human brain | journal = Brain Research | volume = 662 | issue = 1–2 | pages = 245–50 | date = October 1994 | pmid = 7859077 | doi = 10.1016/0006-8993(94)90819-2 | s2cid = 35811464 }}
* {{cite journal | vauthors = Kanai Y, Stelzner M, Nussberger S, Khawaja S, Hebert SC, Smith CP, Hediger MA | title = The neuronal and epithelial human high affinity glutamate transporter. Insights into structure and mechanism of transport | journal = The Journal of Biological Chemistry | volume = 269 | issue = 32 | pages = 20599–606 | date = August 1994 | doi = 10.1016/S0021-9258(17)32035-5 | pmid = 7914198 | doi-access = free }}
* {{cite journal | vauthors = Zerangue N, Kavanaugh MP | title = Interaction of L-cysteine with a human excitatory amino acid transporter | journal = The Journal of Physiology | volume = 493 | issue = Pt 2 | pages = 419–23 | date = June 1996 | pmid = 8782106 | pmc = 1158927 | doi = 10.1113/jphysiol.1996.sp021393 }}
* {{cite journal | vauthors = Bar-Peled O, Ben-Hur H, Biegon A, Groner Y, Dewhurst S, Furuta A, Rothstein JD | title = Distribution of glutamate transporter subtypes during human brain development | journal = Journal of Neurochemistry | volume = 69 | issue = 6 | pages = 2571–80 | date = December 1997 | pmid = 9375691 | doi = 10.1046/j.1471-4159.1997.69062571.x | s2cid = 34227788 | doi-access = free }}
* {{cite journal | vauthors = He Y, Janssen WG, Rothstein JD, Morrison JH | title = Differential synaptic localization of the glutamate transporter EAAC1 and glutamate receptor subunit GluR2 in the rat hippocampus | journal = The Journal of Comparative Neurology | volume = 418 | issue = 3 | pages = 255–69 | date = March 2000 | pmid = 10701825 | doi = 10.1002/(SICI)1096-9861(20000313)418:3<255::AID-CNE2>3.0.CO;2-6 | s2cid = 23608989 }}
* {{cite journal | vauthors = Lin CI, Orlov I, Ruggiero AM, Dykes-Hoberg M, Lee A, Jackson M, Rothstein JD | title = Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18 | journal = Nature | volume = 410 | issue = 6824 | pages = 84–8 | date = March 2001 | pmid = 11242046 | doi = 10.1038/35065084 | bibcode = 2001Natur.410...84L | s2cid = 4622513 }}
* {{cite journal | vauthors = Veenstra-VanderWeele J, Kim SJ, Gonen D, Hanna GL, Leventhal BL, Cook EH | title = Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder | journal = Molecular Psychiatry | volume = 6 | issue = 2 | pages = 160–7 | date = March 2001 | pmid = 11317217 | doi = 10.1038/sj.mp.4000806 | s2cid = 13969870 | doi-access =  }}
* {{cite journal | vauthors = Borre L, Kavanaugh MP, Kanner BI | title = Dynamic equilibrium between coupled and uncoupled modes of a neuronal glutamate transporter | journal = The Journal of Biological Chemistry | volume = 277 | issue = 16 | pages = 13501–7 | date = April 2002 | pmid = 11823462 | doi = 10.1074/jbc.M110861200 | doi-access = free }}
* {{cite journal | vauthors = González MI, Bannerman PG, Robinson MB | title = Phorbol myristate acetate-dependent interaction of protein kinase Calpha and the neuronal glutamate transporter EAAC1 | journal = The Journal of Neuroscience | volume = 23 | issue = 13 | pages = 5589–93 | date = July 2003 | pmid = 12843260 | pmc = 6741220 | doi =  10.1523/jneurosci.23-13-05589.2003}}
* {{cite journal | vauthors = Noorlander CW, de Graan PN, Nikkels PG, Schrama LH, Visser GH | title = Distribution of glutamate transporters in the human placenta | journal = Placenta | volume = 25 | issue = 6 | pages = 489–95 | date = July 2004 | pmid = 15135231 | doi = 10.1016/j.placenta.2003.10.018 }}
* {{cite journal | vauthors = Koch HP, Larsson HP | title = Small-scale molecular motions accomplish glutamate uptake in human glutamate transporters | journal = The Journal of Neuroscience | volume = 25 | issue = 7 | pages = 1730–6 | date = February 2005 | pmid = 15716409 | pmc = 6725926 | doi = 10.1523/JNEUROSCI.4138-04.2005 }}
* {{cite journal | vauthors = Vallejo-Illarramendi A, Domercq M, Pérez-Cerdá F, Ravid R, Matute C | title = Increased expression and function of glutamate transporters in multiple sclerosis | journal = Neurobiology of Disease | volume = 21 | issue = 1 | pages = 154–64 | date = January 2006 | pmid = 16061389 | doi = 10.1016/j.nbd.2005.06.017 | s2cid = 17817187 }}
* {{cite journal | vauthors = 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 | display-authors = 6 | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 |  bibcode = 2005Natur.437.1173R | s2cid = 4427026 }}
* {{cite journal | vauthors = Rainesalo S, Keränen T, Saransaari P, Honkaniemi J | title = GABA and glutamate transporters are expressed in human platelets | journal = Brain Research. Molecular Brain Research | volume = 141 | issue = 2 | pages = 161–5 | date = November 2005 | pmid = 16198020 | doi = 10.1016/j.molbrainres.2005.08.013 }}
{{Refend}}

{{NLM content}}
{{Amphetamine}}

[[Category:Solute carrier family]]
[[Category:Neurotransmitter transporters]]



{{Sourceattribution|Excitatory amino acid transporter 3}}