Molecular heterogeneity of the gamma-aminobutyric acid (GABA) transport system. Cloning of two novel high affinity GABA transporters from rat brain

• Published in: The Journal of biological chemistry Vol. 267; no. 29; pp. 21098 - 21104
• Main Authors: BORDEN, L. A, SMITH, K. E, HARTIG, P. R, BRANCHEK, T. A, WEINSHANK, R. L
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 15.10.1992
• Subjects: Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Base Sequence; Binding and carrier proteins; Biological and medical sciences; Brain - metabolism; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Line; Cloning, Molecular; DNA - genetics; Fundamental and applied biological sciences. Psychology; GABA Plasma Membrane Transport Proteins; gamma-Aminobutyric Acid - metabolism; Gene Library; Kinetics; Membrane Proteins; Membrane Transport Proteins; Models, Structural; Molecular Sequence Data; Oligodeoxyribonucleotides; Oligonucleotides, Antisense; Organic Anion Transporters; Polymerase Chain Reaction; Protein Conformation; Proteins; Rats; Sequence Homology, Amino Acid; Substrate Specificity; Transfection; Northern blotting; Vertebrata; Mammalia; Complementary DNA; Rat; Rodentia; GABA; Primary structure; Molecular cloning; Localization; Carrier protein
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(19)36802-4

cDNA clones encoding two novel gamma-aminobutyric acid (GABA) transporters (designated GAT-2 and GAT-3) have been isolated from rat brain, and their functional properties have been examined in mammalian cells. The transporters display high affinity for GABA (Km approximately 10 microM) and exhibit pharmacological properties distinct from the previously cloned neuronal GABA transporter (GAT-1). Both transporters require sodium and chloride for transport activity. The nucleotide sequences of GAT-2 and GAT-3 predict proteins of 602 and 627 amino acids, respectively, which can be modeled with 12 transmembrane domains, similar to the topology proposed for other cloned neurotransmitter transporters. Localization studies indicate that both transporters are present in brain and retina, while GAT-2 is also present in peripheral tissues. The cloning of these transporter genes from rat brain reveals previously undescribed heterogeneity in GABA transporters.