Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family
Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family
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DOI：
10.1038/26246
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发表时间：
1998-09-17
期刊：
影响因子：
64.8
通讯作者：
Verrey, F
中科院分区：
文献类型：
--
作者：
Mastroberardino, L;Spindler, B;Verrey, F
氨基酸跨细胞质膜转运依赖于几个平行功能的（共）转运蛋白和交换蛋白。广泛分布的转运系统L负责大的中性氨基酸的钠非依赖性交换，而系统y（+）L与钠一起交换带正电荷的氨基酸和/或中性氨基酸（2，3）。尽管已知人细胞表面糖蛋白4F 2重链（h4 F2 hc;小鼠中的CD 98）（4，5）的表达可诱导低水平的L-和/或γ（+）L-型转运（6-9），但这些转运蛋白的分子性质仍不清楚。该糖蛋白存在于活化的淋巴细胞中，同时存在一种表观相对分子质量为40，000（M-r 40 K）的未表征的二硫键连接亲脂性轻链（10，11）。在这里，我们确定了通透酶相关蛋白E16（参考文献12）作为h4 F2 hc的第一条轻链，并表明所产生的异二聚体复合物介导L型氨基酸转运。曼氏血吸虫的同源蛋白SPRM 1也与共表达的h4 F2 hc糖蛋白共价结合，尽管它诱导不同底物特异性的氨基酸转运。h4 F2 hc的共表达是这些通透酶相关轻链的表面表达所必需的，这些轻链属于与细胞表面糖蛋白形成异源二聚体的氨基酸转运蛋白的新家族。
Amino-acid transport across cellular plasma membranes depends on several parallel-functioning (co-)transporters and exchangers'. The widespread transport system L accounts for a sodium-independent exchange of large, neutral amino acids, whereas the system y(+)L exchanges positively charged amino acids and/or neutral amino acids together with sodium(2,3). The molecular nature of these transporters remains unknown, although expression of the human cell-surface glycoprotein 4F2 heavy chain (h4F2hc; CD98 in the mouse)(4,5) is known to induce low levels of L- and/or y(+)L-type transport(6-9). This glycoprotein is found in activated lymphocytes, together with an uncharacterized, disulphide-linked lipophilic light chain with an apparent relative molecular mass of 40,000 (M-r 40 K)(10,11). Here we identify the permease-related protein E16 (ref. 12) as the first light chain of h4F2hc and show that the resulting heterodimeric complex mediates L-type amino-acid transport. The homologous protein from Schistosoma mansoni, SPRM1, also associates covalently with coexpressed h4F2hc glycoprotein, although it induces amino-acid transport of different substrate specificity. The coexpression of h4F2hc is required for surface expression of these permease-related light chains, which belong to a new family of amino-acid transporters that form heterodimers with cell-surface glycoproteins.