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在人脑中表达的支链氨基酸转运体SBAT1(SLC6A15)的特性分析。

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

作者信息

Takanaga Hitomi, Mackenzie Bryan, Peng Ji-Bin, Hediger Matthias A

机构信息

Membrane Biology Program and Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

出版信息

Biochem Biophys Res Commun. 2005 Nov 25;337(3):892-900. doi: 10.1016/j.bbrc.2005.09.128. Epub 2005 Sep 30.

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.

摘要

SLC6基因家族由转运神经递质、氨基酸或渗透溶质的膜蛋白组成。我们报告了人类SLC6A15基因的首次功能特性,该基因编码一种钠偶联支链氨基酸转运体1(SBAT1)。SBAT1的表达在大脑中具有特异性。当在非洲爪蟾卵母细胞中表达时,SBAT1介导疏水性两性离子α-氨基酸和亚氨基酸的钠偶联转运。SBAT1对支链氨基酸(BCAA)和蛋氨酸表现出强烈偏好(K0.5为80 - 160微摩尔)。SBAT1排除芳香族或带电荷的氨基酸、β-氨基酸、甘氨酸和γ-氨基丁酸。SBAT1介导的氨基酸或亚氨基酸转运对温度极为敏感(Q10 = 9),且在酸性pH下受到抑制。蛋白激酶C激活减少了SBAT1蛋白在质膜上的数量。SBAT1介导的BCAA转运,尤其是亮氨酸转运,可能是谷氨酸能和γ-氨基丁酸能神经元中神经递质合成的重要氨基氮来源。

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