Publications

• Characterization of a branched-chain amino-acid transporter SBAT1 (SLC6A15) that is expressed in human brain.

  Takanaga H., Mackenzie B., Peng J.B., Hediger M.A.

  The SLC6 gene family comprises membrane proteins that transport neurotransmitters, amino acids, or osmolytes. We report the first functional characterization of the human SLC6A15 gene, which codes for a sodium-coupled branched-chain amino-acid transporter 1 (SBAT1). SBAT1 expression is specific to ... >> More

  The SLC6 gene family comprises membrane proteins that transport neurotransmitters, amino acids, or osmolytes. We report the first functional characterization of the human SLC6A15 gene, which codes for a sodium-coupled branched-chain amino-acid transporter 1 (SBAT1). SBAT1 expression is specific to the brain. When expressed in Xenopus oocytes, SBAT1 mediated Na+-coupled transport of hydrophobic, zwitterionic alpha-amino and imino acids. SBAT1 exhibited a strong preference for branched-chain amino acids (BCAA) and methionine (K0.5 80-160 microM). SBAT1 excluded aromatic or charged amino acids, beta-amino acids, glycine, and GABA. SBAT1-mediated transport of amino or imino acids was extremely temperature-dependent (Q10=9) and was inhibited at acidic pH. PKC activation reduced the plasma-membrane population of SBAT1 protein. SBAT1-mediated transport of BCAA, particularly leucine, may be an important source of amino nitrogen for neurotransmitter synthesis in glutamatergic and GABAergic neurons. << Less

  Biochem. Biophys. Res. Commun. 337:892-900(2005) [PubMed] [EuropePMC]

  This publication is cited by 10 other entries.

• Functional properties and cellular distribution of the system A glutamine transporter SNAT1 support specialized roles in central neurons.

  Mackenzie B., Schaefer M.K.-H., Erickson J.D., Hediger M.A., Weihe E., Varoqui H.

  Glutamine, the preferred precursor for neurotransmitter glutamate and GABA, is likely to be the principal substrate for the neuronal System A transporter SNAT1 in vivo. We explored the functional properties of SNAT1 (the product of the rat Slc38a1 gene) by measuring radiotracer uptake and currents ... >> More

  Glutamine, the preferred precursor for neurotransmitter glutamate and GABA, is likely to be the principal substrate for the neuronal System A transporter SNAT1 in vivo. We explored the functional properties of SNAT1 (the product of the rat Slc38a1 gene) by measuring radiotracer uptake and currents associated with SNAT1 expression in Xenopus oocytes and determined the neuronal-phenotypic and cellular distribution of SNAT1 by confocal laser-scanning microscopy alongside other markers. We found that SNAT1 mediates transport of small, neutral, aliphatic amino acids including glutamine (K0.5 approximately 0.3 mm), alanine, and the System A-specific analogue 2-(methylamino)isobutyrate. Amino acid transport is driven by the Na+ electrochemical gradient. The voltage-dependent binding of Na+ precedes that of the amino acid in a simultaneous transport mechanism. Li+ (but not H+) can substitute for Na+ but results in reduced Vmax. In the absence of amino acid, SNAT1 mediates Na+-dependent presteady-state currents (Qmax approximately 9 nC) and a nonsaturable cation leak with selectivity Na+, Li+ >> H+, K+. Simultaneous flux and current measurements indicate coupling stoichiometry of 1 Na+ per 1 amino acid. SNAT1 protein was detected in somata and proximal dendrites but not nerve terminals of glutamatergic and GABAergic neurons throughout the adult CNS. We did not detect SNAT1 expression in astrocytes but detected its expression on the luminal membranes of the ependyma. The functional properties and cellular distribution of SNAT1 support a primary role for SNAT1 in glutamine transport serving the glutamate/GABA-glutamine cycle in central neurons. Localization of SNAT1 to certain dopaminergic neurons of the substantia nigra and cholinergic motoneurons suggests that SNAT1 may play additional specialized roles, providing metabolic fuel (via alpha-ketoglutarate) or precursors (cysteine, glycine) for glutathione synthesis. << Less

  J. Biol. Chem. 278:23720-23730(2003) [PubMed] [EuropePMC]

  This publication is cited by 9 other entries.

• Mutations in SLC6A19, encoding B(0)AT1, cause Hartnup disorder.

  Kleta R., Romeo E., Ristic Z., Ohura T., Stuart C., Arcos-Burgos M., Dave M.H., Wagner C.A., Camargo S.R.M., Inoue S., Matsuura N., Helip-Wooley A., Bockenhauer D., Warth R., Bernardini I., Visser G., Eggermann T., Lee P., Chairoungdua A., Jutabha P., Babu E., Nilwarangkoon S., Anzai N., Kanai Y., Verrey F., Gahl W.A., Koizumi A.

  Hartnup disorder, an autosomal recessive defect named after an English family described in 1956 (ref. 1), results from impaired transport of neutral amino acids across epithelial cells in renal proximal tubules and intestinal mucosa. Symptoms include transient manifestations of pellagra (rashes), ... >> More

  Hartnup disorder, an autosomal recessive defect named after an English family described in 1956 (ref. 1), results from impaired transport of neutral amino acids across epithelial cells in renal proximal tubules and intestinal mucosa. Symptoms include transient manifestations of pellagra (rashes), cerebellar ataxia and psychosis. Using homozygosity mapping in the original family in whom Hartnup disorder was discovered, we confirmed that the critical region for one causative gene was located on chromosome 5p15 (ref. 3). This region is homologous to the area of mouse chromosome 13 that encodes the sodium-dependent amino acid transporter B(0)AT1 (ref. 4). We isolated the human homolog of B(0)AT1, called SLC6A19, and determined its size and molecular organization. We then identified mutations in SLC6A19 in members of the original family in whom Hartnup disorder was discovered and of three Japanese families. The protein product of SLC6A19, the Hartnup transporter, is expressed primarily in intestine and renal proximal tubule and functions as a neutral amino acid transporter. << Less

  Nat. Genet. 36:999-1002(2004) [PubMed] [EuropePMC]

  This publication is cited by 13 other entries.