Cloning and Expression of a Rat Brain GABA Transporter

American Association for the Advancement of Science (AAAS) - Tập 249 Số 4974 - Trang 1303-1306 - 1990
John Guastella1, Nathan Nelson2, Hannah Nelson2, Linda Czyzyk1, Shoshi Keynan3, M C Miedel2, Norman Davidson1, Henry A. Lester1, Thomas Stockner3
1Division of Biology, California Institute of Technology, Pasadena, CA 91125
2Miedel, Roche Institute of Molecular Biology, Roche Research Center, Nutley, NJ 07110.
3Department of Biochernistry, Hadassah Medical School, Hebrew University, Jerusalem, Israel.

Tóm tắt

A complementary DNA clone (designated GAT-1) encoding a transporter for the neurotransmitter γ-aminobutyric acid (GABA) has been isolated from rat brain, and its functional properties have been examined in Xenopus oocytes. Oocytes injected with GAT-1 synthetic messenger RNA accumulated [ 3 H]GABA to levels above control values. The transporter encoded by GAT-1 has a high affinity for GABA, is sodium-and chloride-dependent, and is pharmacologically similar to neuronal GABA transporters. The GAT-1 protein shares antigenic determinants with a native rat brain GABA transporter. The nucleotide sequence of GAT-1 predicts a protein of 599 amino acids with a molecular weight of 67 kilodaltons. Hydropathy analysis of the deduced protein suggests multiple transmembrane regions, a feature shared by several cloned transporters; however, database searches indicate that GAT-1 is not homologous to any previously identified proteins. Therefore, GAT-1 appears to be a member of a previously uncharacterized family of transport molecules.

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Tài liệu tham khảo

AUFFRAY, C, PURIFICATION OF MOUSE IMMUNOGLOBULIN HEAVY-CHAIN MESSENGER-RNAS FROM TOTAL MYELOMA TUMOR RNA, EUROPEAN JOURNAL OF BIOCHEMISTRY 107: 303 (1980).

BLAKELY, R.D., EXPRESSION OF NEUROTRANSMITTER TRANSPORT FROM RAT-BRAIN MESSENGER-RNA IN XENOPUS-LAEVIS OOCYTES, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 85: 9846 (1988).

BOWERY, N.G., SELECTIVE-INHIBITION OF NEURONAL GABA UPTAKE BY CIS-1,3-AMINOCYCLOHEXANE CARBOXYLIC-ACID, NATURE 264: 281 (1976).

10.1016/0003-2697(87)90021-2

10.1016/0022-2836(84)90309-7

GRENNINGLOH, G, THE STRYCHNINE-BINDING SUBUNIT OF THE GLYCINE RECEPTOR SHOWS HOMOLOGY WITH NICOTINIC ACETYLCHOLINE-RECEPTORS, NATURE 328: 215 (1987).

GUASTELLA J unpublished data.

10.1038/330379a0

HOSHINO, T, CLONING AND NUCLEOTIDE-SEQUENCE OF THE GENE BRAB CODING FOR THE SODIUM-COUPLED BRANCHED-CHAIN AMINO-ACID CARRIER IN PSEUDOMONAS-AERUGINOSA PAO, MOLECULAR & GENERAL GENETICS 220: 461 (1990).

IVERSEN, L.L., UPTAKE AND METABOLISM OF GAMMA-AMINOBUTYRIC ACID BY NEURONS AND GLIAL CELLS, BIOCHEMICAL PHARMACOLOGY 24: 933 (1975).

KANNER, B.I., ACTIVE-TRANSPORT OF GAMMA-AMINOBUTYRIC ACID BY MEMBRANE-VESICLES ISOLATED FROM RAT-BRAIN, BIOCHEMISTRY 17: 1207 (1978).

KANNER, B.I., STRUCTURAL AND FUNCTIONAL-STUDIES ON THE SODIUM-COUPLED AND CHLORIDE-COUPLED GAMMA-AMINOBUTYRIC ACID TRANSPORTER - DEGLYCOSYLATION AND LIMITED PROTEOLYSIS, BIOCHEMISTRY 28: 3722 (1989).

KOPITO, R.R., REGULATION OF INTRACELLULAR PH BY A NEURONAL HOMOLOG OF THE ERYTHROCYTE ANION-EXCHANGER, CELL 59: 927 (1989).

KOZAK, M, POINT MUTATIONS DEFINE A SEQUENCE FLANKING THE AUG INITIATOR CODON THAT MODULATES TRANSLATION BY EUKARYOTIC RIBOSOMES, CELL 44: 283 (1986).

10.1093/nar/12.2.857

10.1016/0022-2836(82)90515-0

10.1038/227680a0

LODISH, H.F., MULTI-SPANNING MEMBRANE-PROTEINS - HOW ACCURATE ARE THE MODELS, TRENDS IN BIOCHEMICAL SCIENCES 13: 332 (1988).

MANDEL, M, CDNA SEQUENCE ENCODING THE 16-KDA PROTEOLIPID OF CHROMAFFIN GRANULES IMPLIES GENE DUPLICATION IN THE EVOLUTION OF H+-ATPASES, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 85: 5521 (1988).

MARTIN, D, GABA NERVOUS SYSTEM: 357 (1976).

NAKAO, T, NUCLEOTIDE-SEQUENCE OF PUTP, THE PROLINE CARRIER GENE OF ESCHERICHIA-COLI-K12, MOLECULAR & GENERAL GENETICS 208: 70 (1987).

RADIAN, R, PURIFICATION AND IDENTIFICATION OF THE FUNCTIONAL SODIUM-COUPLED AND CHLORIDE-COUPLED GAMMA-AMINOBUTYRIC-ACID TRANSPORT GLYCOPROTEIN FROM RAT-BRAIN, JOURNAL OF BIOLOGICAL CHEMISTRY 261: 15437 (1986).

SARDET, C, MOLECULAR-CLONING, PRIMARY STRUCTURE, AND EXPRESSION OF THE HUMAN GROWTH FACTOR-ACTIVATABLE NA+/H+ ANTIPORTER, CELL 56: 271 (1989).

SCHOFIELD, P.R., SEQUENCE AND FUNCTIONAL EXPRESSION OF THE GABA-A RECEPTOR SHOWS A LIGAND-GATED RECEPTOR SUPER-FAMILY, NATURE 328: 221 (1987).

SCHON, F, AUTORADIOGRAPHIC LOCALIZATION OF [H-3]GABA AND [H-3]GLUTAMATE OVER SATELLITE GLIAL CELLS, BRAIN RESEARCH 66: 275 (1974).

SCHON, F, CHARACTERIZATION OF [H-3]GABA UPTAKE INTO SATELLITE GLIAL CELLS OF RAT SENSORY GANGLIA, BRAIN RESEARCH 66: 289 (1974).

SCHOUSBOE, A, EFFECTS OF GABA ANALOGS OF RESTRICTED CONFORMATION ON GABA TRANSPORT IN ASTROCYTES AND BRAIN CORTEX SLICES AND ON GABA RECEPTOR-BINDING, JOURNAL OF NEUROCHEMISTRY 33: 181 (1979).

SCHOUSBOE, A, TISSUE DISTRIBUTION, METABOLISM, ANTICONVULSANT EFFICACY, AND EFFECT ON BRAIN AMINO-ACID LEVELS OF THE GLIA-SELECTIVE GAMMA-AMINOBUTYRIC-ACID TRANSPORT INHIBITOR 4,5,6,7-TETRAHYDROISOXAZOLO[4,5-C]PYRIDIN-3-OL IN MICE AND CHICKS, JOURNAL OF NEUROCHEMISTRY 47: 758 (1986).

SNUTCH, T.P., RAT-BRAIN EXPRESSES A HETEROGENEOUS FAMILY OF CALCIUM CHANNELS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 3391 (1990).

VONHEIJNE, G, PATTERNS OF AMINO-ACIDS NEAR SIGNAL-SEQUENCE CLEAVAGE SITES, EUROPEAN JOURNAL OF BIOCHEMISTRY 133: 17 (1983).

WOOD, J.D., A COMPARATIVE-STUDY AND PARTIAL CHARACTERIZATION OF MULTI-UPTAKE SYSTEMS FOR GAMMA-AMINOBUTYRIC-ACID, JOURNAL OF NEUROCHEMISTRY 49: 1202 (1987).

ZALESKA, M.M., ROLE OF SIALIC-ACID IN SYNAPTOSOMAL TRANSPORT OF AMINO-ACID TRANSMITTERS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 84: 1709 (1987).

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American Association for the Advancement of Science (AAAS)

Tập 249 Số 4974

1303-1306

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