System L: heteromeric exchangers of large, neutral amino acids involved in directional transport
System L: heteromeric exchangers of large, neutral amino acids involved in directional transport
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DOI：
10.1007/s00424-002-0973-z
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发表时间：
2003-02-01
影响因子：
4.5
通讯作者：
Verrey, F
中科院分区：
文献类型：
--
作者：
Verrey, F
质膜转运系统L在许多细胞中是输入大支链和芳香族中性氨基酸的唯一（有效）途径。相应的转运蛋白是由与糖蛋白4F 2 hc/CD 98（重链）共价结合的催化亚基（LAT 1或LAT 2 =轻链=糖蛋白相关氨基酸转运蛋白）组成的异（二）聚体。LAT 1的组织分布表明，它主要参与将氨基酸转运到生长的细胞中并穿过一些内皮/上皮分泌屏障，而LAT 2的定位表明，它主要参与经上皮（再）吸收氨基酸的基底外侧流出步骤转运。然而，系统L转运蛋白是具有1：1化学计量的必需氨基酸交换剂，具有相似（但不相同）的细胞内和细胞外底物选择性，并且具有高度不对称的表观亲和力（内部亲和力低）。因此，系统L对大的中性氨基酸的净定向转运依赖于具有重叠选择性的单向转运蛋白（例如系统A或N）的平行表达，该单向转运蛋白提供/取代驱动系统L交换功能的氨基酸。通过调节这些交换底物的流量，单向转运蛋白控制系统L的活性。
The plasma membrane transport system L is in many cells the only (efficient) pathway for the import of large branched and aromatic neutral amino acids. The corresponding transporters are hetero(di)mers composed of a catalytic subunit (LAT1 or LAT2 = light chain = glycoprotein-associated amino acid transporter) associated covalently with the glycoprotein 4F2hc/CD98 (heavy chain). The tissue distribution of LAT1 suggests that it is involved mainly in transporting amino acids into growing cells and across some endothelial/epithelial secretory barriers, whereas the localization of LAT2 indicates that it is mainly involved in the basolateral efflux step of transepithelial (re)absorptive amino acid transport. However, system L transporters are obligatory amino acid exchangers with 1:1 stoichiometry, with similar (but not identical) intra- and extracellular substrate selectivities and with highly asymmetrical apparent affinities (low affinity inside). Therefore, net directional transport of large, neutral amino acids by system L depends on the parallel expression of a unidirectional transporter with overlapping selectivity (for instance systems A or N) that provides/recycles amino acids that drive system L exchange function. By mediating the regulated flux of these exchange substrates, unidirectional transporters control the activity of system L.