SODIUM-COUPLED NEUROTRANSMITTER TRANSPORT - STRUCTURE, FUNCTION AND REGULATION

The removal of neurotransmitters by their transporters - located in th e plasma membranes of nerve terminals and glial cells - plays an impor tant role in the termination of synaptic transmission. In the last 3 y ears, many neurotransmitter transporters have been cloned. Structurall y and functionally they can be divided into two groups: glutamate tran sporters, of which to date three have been cloned, couple the flow of glutamate to that of sodium and potassium. The second group of transpo rters includes those for GABA, glycine, taurine, norepinephrine, dopam ine and serotonin. They are sodium- and chloride-dependent, but do not require potassium for function. One of these, the GABA(A) transporter , encoded by GAT-1, is perhaps the best characterized. It has been pur ified and reconstituted and has a molecular mass of around 80 kDa, of which 10-15 kDa is sugar. Amino and carboxyl termini (around 50 amino acids each) are not required for function. The transporter is protecte d against proteolysis at multiple sites by GABA, provided that the two cosubstrates - sodium and chloride - are present. Several amino acid residues that are critical for function have been identified in the GA BA transporter. These include arginine-69 and tryptophan-222 located i n the first and fourth putative transmembrane helices, respectively. T he first is possibly involved in the binding of chloride. The tryptoph an appears to serve as a binding site for the amino group of GABA.