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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/17 20:38:19」(JST)

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Excitatory amino-acid transporter 2 (EAAT2) also known as solute carrier family 1 member 2 (SLC1A2) is a protein that in humans is encoded by the SLC1A2 gene.^[1]^[2] Alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.^[2]

Function

SLC1A2 / EAAT2 is a member of a family of the solute carrier family of proteins. The membrane-bound protein is the principal transporter that clears the excitatory neurotransmitter glutamate from the extracellular space at synapses in the central nervous system. Glutamate clearance is necessary for proper synaptic activation and to prevent neuronal damage from excessive activation of glutamate receptors.^[2]

Clinical significance

Mutations in and decreased expression of this protein are associated with amyotrophic lateral sclerosis (ALS).^[2] The drug riluzole approved for the treatment of ALS upregulates EAAT2.^[3]

Ceftriaxone, an antibiotic, has been shown to induce/enhance the expression of EAAT2, resulting in reduced glutamate activity.^[4] Ceftriaxone has been shown to reduce the development and expression of tolerance to opiates and other drugs of abuse. EAAT2 may possess an important role in modulating drug addiction and tolerance.^[5]

Upregulation of EAAT2(GLT-1) causes impairment of prepulse inhibition, a sensory gating deficit present in schizophrenics and schizophrenia animal models.^[6]^[7] Some antipsychotics have been shown to reduce the expression of EAAT2.^[8]^[9]

Interactions

SLC1A2 has been shown to interact with JUB.^[10]

As a drug target

EAAT2/GLT-1, being the most abundant subtype of glutamate transporter in the CNS, plays a key role in regulation of glutamate transmission. Dysfunction of EAAT2 has been correlated with various pathologies such as traumatic brain injury, stroke, Amyotrophic lateral sclerosis (ALS), Alzheimer's disease, among others. Therefore, activators of the function or enhancers of the expression of EAAT2/GLT-1 could serve as a potential therapy for these conditions. Translational activators of EAAT2/GLT-1, such as ceftriaxone and LDN/OSU-0212320, have been described to have significant protective effects in animal models of ALS and epilepsy. In addition, pharmacological activators of the activity of EAAT2/GLT-1 have been explored for decades and are currently emerging as promising tools for neuroprotection, having potential advantages over expression activators.^[11]

References

^ Pines G, Danbolt NC, Bjørås M, Zhang Y, Bendahan A, Eide L, Koepsell H, Storm-Mathisen J, Seeberg E, Kanner BI (Dec 1992). "Cloning and expression of a rat brain L-glutamate transporter". Nature 360 (6403): 464–7. doi:10.1038/360464a0. PMID 1448170.
^ ^a ^b ^c ^d "Entrez Gene: SLC1A2 solute carrier family 1 (glial high affinity glutamate transporter), member 2".
^ Carbone M, Duty S, Rattray M (2012). "Riluzole elevates GLT-1 activity and levels in striatal astrocytes". Neurochem. Int. 60 (1): 31–8. doi:10.1016/j.neuint.2011.10.017. PMC 3430367. PMID 22080156.
^ Lee SG, Su ZZ, Emdad L, Gupta P, Sarkar D, Borjabad A, Volsky DJ, Fisher PB (May 2008). "Mechanism of ceftriaxone induction of excitatory amino acid transporter-2 expression and glutamate uptake in primary human astrocytes". J. Biol. Chem. 283 (19): 13116–23. doi:10.1074/jbc.M707697200. PMC 2442320. PMID 18326497.
^ Reissner KJ, Kalivas PW (2010). "Using glutamate homeostasis as a target for treating addictive disorders". Behav Pharmacol 21 (5-6): 514–22. doi:10.1097/FBP.0b013e32833d41b2. PMC 2932669. PMID 20634691.
^ Bellesi M, Melone M, Gubbini A, Battistacci S, Conti F (2009). "GLT-1 upregulation impairs prepulse inhibition of the startle reflex in adult rats". Glia 57 (7): 703–13. doi:10.1002/glia.20798. PMID 18985735.
^ Bellesi M, Conti F (2010). "The mGluR2/3 agonist LY379268 blocks the effects of GLT-1 upregulation on prepulse inhibition of the startle reflex in adult rats". Neuropsychopharmacology 35 (6): 1253–60. doi:10.1038/npp.2009.225. PMC 3055342. PMID 20072121.
^ Schmitt A, Zink M, Petroianu G, May B, Braus DF, Henn FA (2003). "Decreased gene expression of glial and neuronal glutamate transporters after chronic antipsychotic treatment in rat brain". Neurosci. Lett. 347 (2): 81–4. doi:10.1016/S0304-3940(03)00653-0. PMID 12873733.
^ Vallejo-Illarramendi A, Torres-Ramos M, Melone M, Conti F, Matute C (2005). "Clozapine reduces GLT-1 expression and glutamate uptake in astrocyte cultures". Glia 50 (3): 276–9. doi:10.1002/glia.20172. PMID 15739191.
^ Marie H, Billups D, Bedford FK, Dumoulin A, Goyal RK, Longmore GD, Moss SJ, Attwell D (February 2002). "The amino terminus of the glial glutamate transporter GLT-1 interacts with the LIM protein Ajuba". Mol. Cell. Neurosci. 19 (2): 152–64. doi:10.1006/mcne.2001.1066. PMID 11860269.
^ Fontana AC (June 20, 2015). "Current approaches to enhance glutamate transporter function and expression.". J Neurochem. 134: 982–1007. doi:10.1111/jnc.13200. PMID 26096891.

UpToDate Contents

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1. 筋萎縮性側索硬化症の疫学および病因 epidemiology and pathogenesis of amyotrophic lateral sclerosis

English Journal

Astrocyte membrane properties are altered in a rat model of developmental cortical malformation but single-cell astrocytic glutamate uptake is robust.

Hanson E1, Danbolt NC2, Dulla CG1.
Neurobiology of disease.Neurobiol Dis.2016 May;89:157-68. doi: 10.1016/j.nbd.2016.02.012. Epub 2016 Feb 10.
Developmental cortical malformations (DCMs) are linked with severe epilepsy and are caused by both genetic and environmental insults. DCMs include several neurological diseases, such as focal cortical dysplasia, polymicrogyria, schizencephaly, and others. Human studies have implicated astrocyte reac
PMID 26875663

Effects of ceftriaxone on ethanol, nicotine or sucrose intake by alcohol-preferring (P) rats and its association with GLT-1 expression.

Sari Y1, Toalston JE2, Rao PS3, Bell RL4.
Neuroscience.Neuroscience.2016 Apr 6. pii: S0306-4522(16)30059-8. doi: 10.1016/j.neuroscience.2016.04.004. [Epub ahead of print]
Increased glutamatergic neurotransmission appears to mediate the reinforcing properties of drugs of abuse, including ethanol (EtOH). We have shown that administration of ceftriaxone (CEF), a β-lactam antibiotic, reduced EtOH intake and increased glutamate transporter 1 (GLT-1) expression in mesocor
PMID 27060486

Effects of Glycyrrhetinic Acid on GSH Synthesis Induced by Realgar in the Mouse Hippocampus: Involvement of System [Formula: see text], System [Formula: see text], MRP-1, and Nrf2.

Wang YL1,2, Chen M1, Huo TG1, Zhang YH1, Fang Y1,3, Feng C1, Wang SY1,4, Jiang H5.
Molecular neurobiology.Mol Neurobiol.2016 Apr 2. [Epub ahead of print]
Realgar, a type of mineral drug-containing arsenic, exhibits neurotoxicity. Brain glutathione (GSH) is crucial to protect the nervous system and to resist arsenic toxicity. Therefore, the main aim of this study was to explore the neurotoxic mechanisms of realgar and the protective effects of glycyrr
PMID 27039309

Japanese Journal

イヌ興奮性アミノ酸輸送体5のクローニングと初代レンズ上皮細胞での検出

落合秀治,齋藤弥代子,圓尾拓也 [他],KANEMAKI Nobuyuki
Experimental Animals 59(4), 449-457, 2010
… In canine, EAAT5 has a 49.4% identity with EAAT1, 43.7% with EAAT2, 46.4% with EAAT3, and 45.7% with EAAT4. …
NAID 130000298605

Impaired Expression of Excitatory Amino Acid Transporter 2 (EAAT2) and Glutamate Homeostasis in Canine Necrotizing Meningoencephalitis(Clinical Pathology)

Pham Ngoc-Thi,Matsuki Naoaki,Shibuya Masahiro [他],TAMAHARA Satoshi,ONO Kenichiro
The journal of veterinary medical science 70(10), 1071-1075, 2008-10-25
… Simultaneously, expression of excitatory amino acid transporter 2 (EAAT2) mRNA was significantly reduced in the astrocytes without change in EAAT1 mRNA. … Hence, reduced expression of EAAT2 and impaired glutamate homeostasis may contribute to the pathogenesis of NME. …
NAID 110006967090

Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS)

HOWLAND DS
Proc Natl Acad Sci USA 99, 1604-1609, 2002
NAID 30016223559

Related Pictures

★リンクテーブル★

リンク元	「興奮性アミノ酸トランスポーター2」「GLT-1」「excitatory amino acid transporter 2」「2型興奮性アミノ酸輸送体」
関連記事	「EAAT」「EAA」

「興奮性アミノ酸トランスポーター2」

Solute carrier family 1 (glial high affinity glutamate transporter), member 2
Identifiers
Symbols	SLC1A2 ; EAAT2; GLT-1; HBGT
External IDs	OMIM: 600300 MGI: 101931 HomoloGene: 3075 ChEMBL: 4973 GeneCards: SLC1A2 Gene
Gene ontology
Molecular function	• L-glutamate transmembrane transporter activity; • protein binding; • glutamate:sodium symporter activity; • sodium:dicarboxylate symporter activity;
Cellular component	• plasma membrane; • cell surface; • membrane; • integral component of membrane; • axolemma;
Biological process	• ion transport; • synaptic transmission; • neurotransmitter secretion; • visual behavior; • response to wounding; • multicellular organismal aging; • glutamate secretion; • telencephalon development; • adult behavior; • cellular response to extracellular stimulus; • multicellular organism growth; • response to drug; • response to amino acid; • positive regulation of glucose import; • L-glutamate import; • transmembrane transport; • D-aspartate import; • L-glutamate transmembrane transport;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;