Characterization of a branched-chain amino-acid transporter SBAT1 (SLC6A15) that is expressed in human brain.
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.
Takanaga
Hitomi
H
Membrane Biology Program and Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Mackenzie
Bryan
B
Peng
Ji-Bin
JB
Hediger
Matthias A
MA
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*
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