A new family of neurotransmitter transporters: The high-affinity glutamate transporters

An essential component of the transmission process at glutamatergic synapses is the removal of glutamate from the synaptic cleft. This is achieved by powerful transport systems which have a high affinity for glutamate and exhibit a novel coupling to inorganic ions. Transporters situated on presynaptic termini sequester glutamate directly from the synaptic cleft. In concert, transporters situated on glial cells maintain a low extracellular glutamate concentration, thereby establishing a diffusion gradient favoring movement of glutamate out of the synaptic cleft. Maintenance of a low extracellular glutamate concentration also serves to protect neurons from the excitotoxic action of glutamate. Despite the physiological importance of the glutamate transporters, little information has been available on their molecular structures. This gap, however, has begun to be bridged with the recent cloning of three species of eukaryotic glutamate transporters. The purpose of this review is to summarize the results of these three cloning successes, to compare and contrast the three novel transporters, and to reinterpret, in the light of these recent breakthroughs, information from previous studies.