title: Characterization of a branched-chain amino-acid transporter SBAT1 (SLC6A15) that is expressed in human brain.
abstract: 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.
authors.affiliation: Membrane Biology Program and Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Takanaga
authors.forename: Bryan
authors.initials: B
authors.lastname: Mackenzie
authors.forename: Ji-Bin
authors.initials: JB
authors.lastname: Peng
authors.forename: Matthias A
authors.initials: MA
authors.lastname: Hediger
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000032:analysis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002478:Cells, Cultured; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology; D021381:Protein Transport / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D000597:Amino Acids, Branched-Chain; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; C506212:SLC6A15 protein, human; D005680:gamma-Aminobutyric Acid; D012964:Sodium