Structure and Function of Sodium-Coupled Neurotransmitter Transporters

Abstract

The removal of neurotransmitters by their transporters-located in the plasma membranes of nerve terminals and glial cells – plays an important role in the termination of synaptic transmission. In the last 3 years many neurotransmitter transporters have been cloned. Structurally and functionally they can be divided into two groups: glutamate transporters, of which to date three have been cloned, couple the flow of glutamate to that of sodium and potassium. The second group of transporters includes those for γ-aminobutyric acid (GABAa), glycine, taurine, norepinephrine, dopamine and serotonin. They are sodium- and chloride-dependent, but do not require potassium for function. One of these, the GABAA transporter, encoded by GAT-1, is perhaps the best characterized. It has been purified and reconstituted and has a molecular mass of around 80 kD, of which 10–15 kD is sugar. Amino- and carboxyltermini (around 50 amino acids each) are not required for function. The transporter is protected against proteolysis at multiple sites by GABA, provided that the two cosubstrates -sodium and chloride – are present. Several amino acid residues, which are critical for function, have been identified in the GABA and dopamine transporters.