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Review
. 2014 Jun;71(11):2001-15.
doi: 10.1007/s00018-013-1484-0. Epub 2013 Oct 26.

Changes in the expression of the glutamate transporter EAAT3/EAAC1 in health and disease

Massimiliano G Bianchi  1 , Donatella Bardelli, Martina Chiu, Ovidio Bussolati
Affiliations
Review

Changes in the expression of the glutamate transporter EAAT3/EAAC1 in health and disease

Massimiliano G Bianchi et al. Cell Mol Life Sci. 2014 Jun.

Abstract

Excitatory amino acid transporters (EAATs) are high-affinity Na(+)-dependent carriers of major importance in maintaining glutamate homeostasis in the central nervous system. EAAT3, the human counterpart of the rodent excitatory amino acid carrier 1 (EAAC1), is encoded by the SLC1A1 gene. EAAT3/EAAC1 is ubiquitously expressed in the brain, mostly in neurons but also in other cell types, such as oligodendrocyte precursors. While most of the glutamate released in the synapses is taken up by the "glial-type" EAATs, EAAT2 (GLT-1 in rodents) and EAAT1 (GLAST), the functional role of EAAT3/EAAC1 is related to the subtle regulation of glutamatergic transmission. Moreover, because it can also transport cysteine, EAAT3/EAAC1 is believed to be important for the synthesis of intracellular glutathione and subsequent protection from oxidative stress. In contrast to other EAATs, EAAT3/EAAC1 is mostly intracellular, and several mechanisms have been described for the rapid regulation of the membrane trafficking of the transporter. Moreover, the carrier interacts with several proteins, and this interaction modulates transport activity. Much less is known about the slow regulatory mechanisms acting on the expression of the transporter, although several recent reports have identified changes in EAAT3/EAAC1 protein level and activity related to modulation of its expression at the gene level. Moreover, EAAT3/EAAC1 expression is altered in pathological conditions, such as hypoxia/ischemia, multiple sclerosis, schizophrenia, and epilepsy. This review summarizes these results and provides an overall picture of changes in EAAT3/EAAC1 expression in health and disease.

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Figures

Fig. 1
Fig. 1
Sites of regulation of EAAT3/EAAC1 expression on the plasma membrane. The sketch depicts the three documented sites of regulation of EAAT3/EAAC1 expression: changes in SLC1A1 transcription, modulation of carrier interaction with binding proteins and modification of transporter trafficking to and from the plasma membrane. For changes in SLC1A1 transcription, transcription factors, chromatin-modifying enzymes, and extracellular stimuli known to be involved in expression changes are detailed
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