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

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.

Integrated Genomics Reveals Convergent Transcriptomic Networks Underlying Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis

“…Specifically of interest is MIR96, which goes up in both diseases and could regulate a number of genes differentially expressed in both IPF and emphysema including SCL1A1, SH3BP5, LDB2, and ARGHAP24. SCL1A1 is a glutamate transporter that is down-regulated under hypoxic conditions (46,47). SH3BP5 inhibits BTK (48), which is a binding partner of hypoxia-induced mitogenic factor (HIMF) (49).…”

Astrogliosis

“…Thus, different signaling mechanisms regulate different aspects of pro-or anti-inflammatory functions of reactive astrocytes. From a different perspective, expression and function of the glutamate transporter GLT-1 can be modulated up or down during astrogliosis depending on the nature of the insult and time after the insult, and this regulation can impact outcome by influencing extracellular glutamate levels and the potential for neuronal excitotoxicity (Bianchi et al 2013). The mTORAkt-NF-kB pathway is one molecular signaling mechanism that can modulate astrocyte expression of Glt-1 (Pawlak et al 2005;Faideau et al 2010;Ji et al 2013).…”

Gene Expression Patterns in Functionally Different Cochlear Compartments of the Newborn Rat

“…Activities that are essential to the maintenance of life should be able to function at lower energy charge values (Atkinson, according to Buttgereit & Brand, 1995;Wieser & Krumschnabel, 2001). Whereas the changes of most of the transcripts may be advantageous for cell survival, the down-regulation of the glial high affinity glutamate transporter Slc1a3 appears to exert a rather damaging effect, in particular in the MOD region, because this strong expression decrease of Slc1a3 may contribute to elevated extracellular glutamate concentrations and cell damage in the MOD region (Bianchi, Bardelli, Chiu, & Bussolati, 2014;Gegelashvili & Schousboe, 1997).…”