Glutamate transporters EAAT2

Excitotoxicity (see Chs 15 and 32) has been suggested to be a mechanism by which motor neurons are damaged in ALS [25,48,49]. About 60-70% of sporadic ALS patients have a 30-95% reduction in the levels of the astroglial glutamate transporter EAAT2 (excitatory amino acid transporter 2), also termed GLT-1, in motor cortex and spinal cord [25, 48, 49]. Reduction in level of activity of this major glutamate transporter leads to increased extracellular concentrations of glutamate at synapses and evidence of excitotoxicity exists in some patients with ALS. 

Otis, T. S. and Kavanaugh, M. R (2000) Isolation of current components and partial reaction cycles in the glial glutamate transporter EAAT2 J. Neurosci. 20,2749-2757. 

Chen Y. and Swanson R. A. (2003). The glutamate transporters EAAT2 and EAAT3 mediate cysteine uptake in cortical neuron cultures. J. Neurochem. 84 1332-1339. 

Suchak, S. K., Baloyianni, N. V., Perkinton, M. S., Williams, R. J., Meldrum, B. S., and Rattray, M. (2003). The glial glutamate transporter, EAAT2 (Git-1) accounts for high affinity glutamate uptake into adult rodent nerve endings. J. Neurochem. 84, 522-532. 

Howland DS, Liu J, She Y, Goad B, MaragaMs NJ, Kim B, Erickson J, Kulik J, DeVito L, Psaltis G, DeGennaro LJ, Cleveland DW, Rothstein JD (2002) Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SODl mutant-mediated amyotrophic lateral sclerosis... 

Aoki M, Lin CL, Rothstein JD, Geller BA, Hosier BA, Munsat TL, Hoiwitz HR, Brown RH, Jr. (1998) Mutadons in the glutamate transporter EAAT2 gene do not cause abnormal EAAT2 transcripts hr amyodophic lateral sclerosis. Ann Neurol 43 645-653. 

Lopez-Redondo F, Nakajima K, Honda S, Kohsaka S (1999) Microglia express the glutamate transporter EAAT2/GLT. J Neurochem 73 (suppl) S91. 

Milton ID, Banner SJ, Ince PG, Piggott NH, Fray AE, Thatcher N, Horne CHW, Shaw PJ (1997) Expression of the glial glutamate transporter EAAT2 in the human CNS an immunohistochemical study. Mol Brain Res 52 17-31. 

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 1082-1088... 

Hoogland G, van Oort RJ, Proper EA et al (2004) Alternative splicing of glutamate transporter EAAT2 RNA in neocortex and hippocampus of temporal lobe epilepsy patients. Epilepsy Res 59 75-82... 

---