Mastroberardino L, Spindler B, Pfeiffer R, Skelly P J, Loffing J, Shoemaker C B, Verrey F
Institute of Physiology, University of Zürich, Switzerland.
Nature. 1998 Sep 17;395(6699):288-91. doi: 10.1038/26246.
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. The molecular nature of these transporters remains unknown, although expression of the human cell-surface glycoprotein 4F2 heavy chain (h4F2hc; CD98 in the mouse) is known to induce low levels of L- and/or y(+)L-type transport. 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) 40K). Here we identify the permease-related protein E16 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.
氨基酸跨细胞质膜的转运依赖于几种并行发挥作用的（共）转运体和交换体。广泛存在的L转运系统介导大的中性氨基酸的非钠依赖性交换，而y(+)L系统则与钠一起交换带正电荷的氨基酸和/或中性氨基酸。尽管已知人细胞表面糖蛋白4F2重链（h4F2hc；小鼠中的CD98）的表达可诱导低水平的L型和/或y(+)L型转运，但这些转运体的分子本质仍不清楚。这种糖蛋白存在于活化的淋巴细胞中，与一种未鉴定的、二硫键连接的亲脂性轻链一起，其表观相对分子质量为40,000（Mr 40K）。在这里，我们鉴定出通透酶相关蛋白E16是h4F2hc的第一条轻链，并表明由此形成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SPRM1也与共表达的h4F2hc糖蛋白共价结合，尽管它诱导的氨基酸转运具有不同的底物特异性。这些通透酶相关轻链的表面表达需要h4F2hc的共表达，它们属于一个新的氨基酸转运体家族，可与细胞表面糖蛋白形成异二聚体。
