SLC1A2

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Solute carrier family 1 (glial high affinity glutamate transporter), member 2
Identifiers
Symbols SLC1A2 ; EAAT2; GLT-1
External IDs OMIM600300 MGI101931 HomoloGene3075 ChEMBL: 4973 GeneCards: SLC1A2 Gene
RNA expression pattern
PBB GE SLC1A2 208389 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 6506 20511
Ensembl ENSG00000110436 ENSMUSG00000005089
UniProt P43004 P43006
RefSeq (mRNA) NM_001195728 NM_001077514
RefSeq (protein) NP_001182657 NP_001070982
Location (UCSC) Chr 11:
35.27 – 35.44 Mb
Chr 2:
102.66 – 102.79 Mb
PubMed search [1] [2]

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[edit]

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[edit]

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[edit]

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

See also[edit]

References[edit]

  1. ^ Pines G, Danbolt NC, Bjoras 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. 
  2. ^ a b c d "Entrez Gene: SLC1A2 solute carrier family 1 (glial high affinity glutamate transporter), member 2". 
  3. ^ 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. PMID 22080156. 
  4. ^ 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. 
  5. ^ 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. PMID 20634691. 
  6. ^ 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. 
  7. ^ 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. PMID 20072121. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 

Further reading[edit]

  • Wang Z, Trillo-Pazos G, Kim SY, et al. (2004). "Effects of human immunodeficiency virus type 1 on astrocyte gene expression and function: potential role in neuropathogenesis.". J. Neurovirol. 10. Suppl 1: 25–32. PMID 14982736. 
  • Arriza JL, Fairman WA, Wadiche JI, et al. (1994). "Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex.". J. Neurosci. 14 (9): 5559–69. PMID 7521911. 
  • Manfras BJ, Rudert WA, Trucco M, Boehm BO (1994). "Cloning and characterization of a glutamate transporter cDNA from human brain and pancreas.". Biochim. Biophys. Acta 1195 (1): 185–8. doi:10.1016/0005-2736(94)90026-4. PMID 7522567. 
  • Li X, Francke U (1995). "Assignment of the gene SLC1A2 coding for the human glutamate transporter EAAT2 to human chromosome 11 bands p13-p12.". Cytogenet. Cell Genet. 71 (3): 212–3. doi:10.1159/000134111. PMID 7587378. 
  • Shashidharan P, Wittenberg I, Plaitakis A (1994). "Molecular cloning of human brain glutamate/aspartate transporter II.". Biochim. Biophys. Acta 1191 (2): 393–6. doi:10.1016/0005-2736(94)90192-9. PMID 8172925. 
  • Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction.". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474. 
  • Yu W, Andersson B, Worley KC, et al. (1997). "Large-scale concatenation cDNA sequencing.". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174. 
  • Milton ID, Banner SJ, Ince PG, et al. (1998). "Expression of the glial glutamate transporter EAAT2 in the human CNS: an immunohistochemical study.". Brain Res. Mol. Brain Res. 52 (1): 17–31. doi:10.1016/S0169-328X(97)00233-7. PMID 9450673. 
  • Shimamoto K, Lebrun B, Yasuda-Kamatani Y, et al. (1998). "DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters.". Mol. Pharmacol. 53 (2): 195–201. PMID 9463476. 
  • Lin CL, Bristol LA, Jin L, et al. (1998). "Aberrant RNA processing in a neurodegenerative disease: the cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis.". Neuron 20 (3): 589–602. doi:10.1016/S0896-6273(00)80997-6. PMID 9539131. 
  • Aoki M, Lin CL, Rothstein JD, et al. (1998). "Mutations in the glutamate transporter EAAT2 gene do not cause abnormal EAAT2 transcripts in amyotrophic lateral sclerosis.". Ann. Neurol. 43 (5): 645–53. doi:10.1002/ana.410430514. PMID 9585360. 
  • Trotti D, Aoki M, Pasinelli P, et al. (2001). "Amyotrophic lateral sclerosis-linked glutamate transporter mutant has impaired glutamate clearance capacity.". J. Biol. Chem. 276 (1): 576–82. doi:10.1074/jbc.M003779200. PMID 11031254. 
  • Münch C, Schwalenstöcker B, Hermann C, et al. (2001). "Differential RNA cleavage and polyadenylation of the glutamate transporter EAAT2 in the human brain.". Brain Res. Mol. Brain Res. 80 (2): 244–51. doi:10.1016/S0169-328X(00)00139-X. PMID 11038258. 
  • Honig LS, Chambliss DD, Bigio EH, et al. (2000). "Glutamate transporter EAAT2 splice variants occur not only in ALS, but also in AD and controls.". Neurology 55 (8): 1082–8. doi:10.1212/wnl.55.8.1082. PMID 11071482. 
  • Flowers JM, Powell JF, Leigh PN, et al. (2001). "Intron 7 retention and exon 9 skipping EAAT2 mRNA variants are not associated with amyotrophic lateral sclerosis.". Ann. Neurol. 49 (5): 643–9. doi:10.1002/ana.1029. PMID 11357955. 
  • Rimaniol AC, Mialocq P, Clayette P, et al. (2001). "Role of glutamate transporters in the regulation of glutathione levels in human macrophages.". Am. J. Physiol., Cell Physiol. 281 (6): C1964–70. PMID 11698255. 
  • Tozaki H, Kanno T, Nomura T, et al. (2002). "Role of glial glutamate transporters in the facilitatory action of FK960 on hippocampal neurotransmission.". Brain Res. Mol. Brain Res. 97 (1): 7–12. doi:10.1016/S0169-328X(01)00304-7. PMID 11744157. 
  • Palmada M, Kinne-Saffran E, Centelles JJ, Kinne RK (2002). "Benzodiazepines differently modulate EAAT1/GLAST and EAAT2/GLT1 glutamate transporters expressed in CHO cells.". Neurochem. Int. 40 (4): 321–6. doi:10.1016/S0197-0186(01)00087-0. PMID 11792462. 
  • Marie H, Billups D, Bedford FK, et al. (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. 
  • Reye P, Sullivan R, Fletcher EL, Pow DV (2002). "Distribution of two splice variants of the glutamate transporter GLT1 in the retinas of humans, monkeys, rabbits, rats, cats, and chickens.". J. Comp. Neurol. 445 (1): 1–12. doi:10.1002/cne.10095. PMID 11891650. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.