Phylogenetic conservation of 4-aminobutyric acid (GABA) transporter isoforms. Cloning and pharmacological characterization of a GABA/beta-alanine transporter from Torpedo.
A family of structurally related, Na+/Cl(-)-dependent plasma-membrane transporters catalyze the uptake of several neurotransmitters, osmolytes and other metabolites into cells. Four different members of this transporter family have been cloned from mammalian sources which all transport 4-aminobutyric acid (GABA) but differ in their pharmacological profiles and in their tissue distribution. We report on the cloning, sequencing and functional expression of a transporter for GABA and beta-alanine from the electric lobe of Torpedo. According to similarity of amino acid sequence (77% identity), pharmacological properties, and tissue distribution (nervous-system-specific), it appears to be the counterpart of the beta-alanine-sensitive GABA transporter, GAT-B/GAT-3/GAT4, previously cloned from rat and mouse. The identification of another GABA transporter isoform from Torpedo (after the recent characterization of a Torpedo GAT-1 transporter) indicates that GABA-transporter isoforms are phylogenetically ancient and arose before the divergence of vertebrates. Sequence comparison between isofunctional transporters from evolutionarily distant species aids in the identification of amino acid residues that are critical for functional specificity. The expression of transporters for GABA and beta-alanine raises questions regarding the unidentified physiological role of these amino acids in Torpedo electric lobe.
Guimbal
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C
Institut für Physiologische Chemie, Medizinische Fakultät, Ruhr-Universität Bochum, Germany.
Klostermann
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A
Kilimann
M W
MW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D004285:Dogs; D029941:Fish Proteins; D018756:GABA Antagonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008969:Molecular Sequence Data; D027361:Organic Anion Transporters; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D016415:Sequence Alignment; D013045:Species Specificity; D013379:Substrate Specificity; D014018:Tissue Distribution; D014101:Torpedo / Q000378:metabolism*; D015091:beta-Alanine / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002352:Carrier Proteins; D029941:Fish Proteins; D018756:GABA Antagonists; D050485:GABA Plasma Membrane Transport Proteins; C098020:GABA-beta-alanine transporter protein, Torpedo marmorata; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C493414:Slc6a1 protein, mouse; C493415:Slc6a1 protein, rat; D015091:beta-Alanine; D005680:gamma-Aminobutyric Acid