Sodium-coupled neurotransmitter transport: structure, function and regulation.
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 GABA, 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 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 protected 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 GABA transporter. These include arginine-69 and tryptophan-222 located in the first and fourth putative transmembrane helices, respectively. The first is possibly involved in the binding of chloride. The tryptophan appears to serve as a binding site for the amino group of GABA.
Kanner
B I
BI
Department of Biochemistry, Hadassah Medical School, Hebrew University, Jerusalem, Israel.
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D050485:GABA Plasma Membrane Transport Proteins; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D026901:Membrane Transport Proteins; D008959:Models, Neurological; D009411:Nerve Endings / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D027361:Organic Anion Transporters; D017433:Protein Structure, Secondary; D012964:Sodium / Q000378:metabolism*; D009435:Synaptic Transmission
D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D018377:Neurotransmitter Agents; D027361:Organic Anion Transporters; C493413:SLC6A1 protein, human; D012964:Sodium