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

被引:72
作者
Takanaga, H
Mackenzie, B
Peng, JB
Hediger, MA [1 ]
机构
[1] Brigham & Womens Hosp, Membrane Biol Program, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Boston, MA 02115 USA
[4] Carnegie Inst Sci, Div Plant Biol, Stanford, CA 94305 USA
[5] Univ Cincinnati, Coll Med, Dept Cellular & Mol Physiol, Cincinnati, OH 45267 USA
[6] Univ Alabama Birmingham, Div Nephrol, Birmingham, AL 35294 USA
[7] Univ Bern, Inst Biochem & Mol Biol, CH-3012 Bern, Switzerland
基金
日本学术振兴会;
关键词
amino acid transport; cotransporters; neurotransmitter synthesis; sodium-dependent transport; Xenopus oocyte;
D O I
10.1016/j.bbrc.2005.09.128
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 I (SBAT1). SBAT1 expression is specific to the brain. When expressed in Xenopus oocytes, SBATI mediated Na+-coupled transport of hydrophobic, zwitterionic a-amino and imino acids. SBAT1 exhibited a strong preference for branched-chain amino acids (BCAA) and methionine (K-0.5 80-160 mu M). SBAT1 excluded aromatic or charged amino acids, P-amino acids, glycine, and GABA. SBAT1-mediated transport of amino or imino acids was extremely temperature-dependent (Q(10) = 9) and was inhibited at acidic pH. PKC activation reduced the plasma-membrane population of SBATI protein. SBAT1-mediated transport of BCAA, particularly leucine, may be an important source of amino nitrogen for neurotransmitter synthesis in glutamatergic and GABAergic neurons. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:892 / 900
页数:9
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