Glutamate transporters: Gene expression regulation and signaling properties

Glutamate is the major excitatory neurotransmitter in the vertebrate central nervous system. During synaptic activity, glutamate is released and binds to specific membrane receptors and transporters activating, in the one hand, a wide variety of signal transduction cascades, while in the other hand, its removal from the synaptic cleft. Extracellular glutamate concentrations are maintained within physiological levels mainly by glia glutamate transporters. Inefficient clearance of this amino acid is neurotoxic due to a prolonged hyperactivation of its postsynaptic receptors, exacerbating a wide array of intracellular events linked to an ionic imbalance, that results in neuronal cell death. This process is known as excitotoxicity and is the underlying mechanisms of an important number of neurodegenerative diseases. Therefore, it is important to understand the regulation of glutamate transporters function. The transporter activity can be regulated at different levels: gene expression, transporter protein targeting and trafficking, and post-translational modifications of the transporter protein. The identification of these mechanisms has paved the way to our current understanding the role of glutamate transporters in brain physiology and will certainly provide the needed biochemical information for the development of therapeutic strategies towards the establishment of novel therapeutic approaches for the treatment and/or prevention of pathologies associated with excitotoxicity insults. This article is part of the issue entitled ‘Special Issue on Neurotransmitter Transporters’. •Plasma membrane Glutamate transporters are regulated at different levels.•Glutamate regulates its own transport.•Glutamate extracellular levels are tightly controlled by its transporters.