Glial Glutamate Transporters as Signaling Molecules.

One of the most important processes of the synaptic transmission is neurotransmitter uptake, which is critical for the good performance of the nervous system by maintaining the neurotransmitter's baseline levels after its release. The major excitatory neurotransmitter in the central nervous system is glutamate; its extracellular levels are tightly regulated through high-affinity plasma membrane transporters. Most of the brain glutamate uptake activity is carried out by glial transporters that until recently have been regarded as important for the recycling of this excitatory amino acid. Besides, a role in the prevention of an overstimulation of neuronal glutamate receptors that would be linked to cell death has been established. Nevertheless, the Na dependence of the uptake process paved the way to the plausible triggering of signal transduction cascades. Over the past decade a considerable amount of evidences suggesting an important intervention of these transporter proteins in glutamate signaling, mainly in glial cells, has been accumulated. Herein we provide a summary or the most important findings in this novel function of glial glutamate transporters as signal transduction entities, as the framework platform through which they may actively participate in glutamate-mediated transactions in the central nervous system.