STRUCTURE AND FUNCTION OF SODIUM-COUPLED NEUROTRANSMITTER TRANSPORTERS

The removal of neurotransmitters by their transporters located in the plasma membranes of nerve terminals and glial cells - plays an importa nt role in the termination of synaptic transmission. In the last 3 yea rs many neurotransmitter transporters have been cloned. Structurally a nd functionally they can be divided into two groups: glutamate transpo rters, of which to date three have been cloned, couple the flow of glu tamate to that of sodium and potassium. The second group of transporte rs includes those for gamma-aminobutyric acid (GABA), glycine, taurine , norepinephrine, dopamine and serotonin. They are sodium- and chlorid e-dependent, but do not require potassium for function. One of these, the GABA(A) transporter, encoded by GAT-1, is perhaps the best charact erized. It has been purified and reconstituted and has a molecular mas s of around 80 kD, of which 10-15 kD is sugar. Amino- and carboxyl-ter mini (around 50 amino acids each) are not required for function. The t ransporter 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 be en identified in the GABA and dopamine transporters.