Transport of D-serine via the amino acid transporter ATB0,+ expressed in the colon
Transport of D-serine via the amino acid transporter ATB0,+ expressed in the colon
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DOI：
10.1006/bbrc.2002.6441
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发表时间：
2002-02-22
影响因子：
3.1
通讯作者：
Ganapathy, V
中科院分区：
文献类型：
--
作者：
Hatanaka, T;Huang, W;Ganapathy, V
D-丝氨酸是脑内内源性合成的一种重要的多巴胺能神经传递调节剂。由于结肠细菌产生D-丝氨酸，我们提出了这样一个问题，即结肠中是否存在可能使这种外源产生的D-丝氨酸可供宿主使用的转运机制。在此，我们首次鉴定了肠道中的氨基酸转运蛋白，用于高亲和力主动转运D-丝氨酸。这种转运蛋白被称为ATB（0，+），是中性和阳离子氨基酸的L-对映体的Na+-和Cl-偶联转运蛋白。在这里，我们证明ATB（0，+）也能够介导Na '-和Cl--偶联转运D-丝氨酸。ATB（0，+）对L-丝氨酸和D-丝氨酸的亲和力相似，两种对映体的Ki值相似于150 μ M。除D-丝氨酸外，ATB（0，+）还转运D-丙氨酸、D-甲硫氨酸、D-亮氨酸和D-色氨酸。然而，其他几种中性和阳离子氨基酸是ATB（0，+）作为L-对映体的可转运底物，当以D-对映体形式存在时，这些氨基酸不被转运。ATB（0，+）在肠道中表达，有趣的是不在近端肠中，而是在远端肠中。表达在结肠中最主要，其中转运蛋白定位于结肠细胞的腔膜，使得该转运蛋白独特地适合于细菌来源的D-丝氨酸的吸收。(C)2002 Elsevier Science（美国）。
D-Serine, synthesized endogenously in the brain, is an important modulator of glutamatergic neurotransmission. Since colonic bacteria produce D-serine, we asked the question whether there are transport mechanisms in the colon that might make this exogenously produced D-serine available to the host. Here we identify for the first time an amino acid transporter in the intestine for high-affinity active transport Of D-serine. This transporter, called ATB(0,+), is a Na+- and Cl--coupled transporter for L-enantiomers of neutral and cationic amino acids. Here we demonstrate that ATB(0,+) is also capable of mediating the Na'- and Cl--coupled transport Of D-serine. The affinity of ATB(0,+) for L-serine and D-serine is similar, the K, value for the two enantiomers being similar to150 muM. In addition to D-serine, ATB(0,+) transports D-alanine, D-methionine, D-leucine, and D-tryptophan. However, several other neutral and cationic amino acids that are transportable substrates for ATB(0,+) as L-enantiomers are not transported when presented as D-enantiomers. ATB(0,+) is expressed in the intestinal tract, interestingly not in the proximal intestine but in the distal intestine. Expression is most predominant in the colon where the transporter is localized to the luminal membrane of colonocytes, making this transporter uniquely suitable for absorption of bacteria-derived D-serine. (C) 2002 Elsevier Science (USA).