Phylogenetic conservation of 4-aminobutyric acid (GABA) transporter isoforms. Cloning and pharmacological characterization of a GABA/beta-alanine transporter from Torpedo.

Publisher: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies Country of Publication: England NLM ID: 0107600 Publication Model: Print Cited Medium: Print ISSN: 0014-2956 (Print) Linking ISSN: 00142956 NLM ISO Abbreviation: Eur J Biochem Subsets: MEDLINE

Publication: -2004: Oxford, UK : Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
Original Publication: Berlin, New York, Springer.

Fish Proteins* ; Membrane Transport Proteins* ; Organic Anion Transporters*; Carrier Proteins/*chemistry ; Membrane Proteins/*chemistry ; Torpedo/*metabolism ; beta-Alanine/*metabolism ; gamma-Aminobutyric Acid/*metabolism; Amino Acid Sequence ; Animals ; Base Sequence ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cell Line ; Cell Membrane/metabolism ; Cloning, Molecular ; Dogs ; GABA Antagonists/pharmacology ; GABA Plasma Membrane Transport Proteins ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice ; Molecular Sequence Data ; Phylogeny ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Rabbits ; Rats ; Sequence Alignment ; Species Specificity ; Substrate Specificity ; Tissue Distribution

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.

GENBANK X87170

0 (Carrier Proteins)
0 (Fish Proteins)
0 (GABA Antagonists)
0 (GABA Plasma Membrane Transport Proteins)
0 (GABA-beta-alanine transporter protein, Torpedo marmorata)
0 (Membrane Proteins)
0 (Membrane Transport Proteins)
0 (Organic Anion Transporters)
0 (RNA, Messenger)
0 (Slc6a1 protein, mouse)
0 (Slc6a1 protein, rat)
11P2JDE17B (beta-Alanine)
56-12-2 (gamma-Aminobutyric Acid)

Date Created: 19951215 Date Completed: 19960311 Latest Revision: 20190620

20231215

10.1111/j.1432-1033.1995.794_a.x

8575437