4F2 (CD98) heavy chain is associated covalently with an amino acid transporter and controls intracellular trafficking and membrane topology of 4F2 heterodimer
4F2 (CD98) heavy chain is associated covalently with an amino acid transporter and controls intracellular trafficking and membrane topology of 4F2 heterodimer
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DOI：
10.1074/jbc.274.5.3009
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发表时间：
1999-01-29
影响因子：
4.8
通讯作者：
Minato, N
中科院分区：
文献类型：
--
作者：
Nakamura, E;Sato, M;Minato, N
4F2，也称为CD98，是一种完整的膜蛋白，由一条重链和一条轻链通过二硫键连接而成。我们制备了针对小鼠4F2轻链的单克隆抗体，并克隆了该单克隆抗体的cDNA，该单克隆抗体编码了大鼠L型氨基酸转运体-1的小鼠对应物，并在4F2重链存在的情况下诱导了爪蟾卵母细胞的系统L氨基酸转运。在哺乳动物细胞中的转染研究表明，4F2重链可以单独在质膜上表达，而4F2轻链只有在4F2重链存在的情况下才能转运到细胞膜表面。4F2重链在成纤维细胞L细胞表面弥散表达，而在表达钙粘蛋白的L细胞中，它选择性地定位于细胞-细胞粘附位点。这些结果表明，4F2重链与氨基酸转运蛋白共价相关，并控制4F2异源二聚体的细胞表面表达和膜拓扑结构。虽然4F2重链和轻链在大多数组织中协调表达，但轻链在肾脏和肠道中几乎不被抗体检测到，尽管重链以复杂的形式存在。结果预测了多个4F2轻链的存在。
4F2, also termed CD98, is an integral membrane protein consisting of a heavy chain linked to a light chain by disulfide bond. We have generated a monoclonal antibody to the mouse 4F2 light chain and cloned the cDNA It encodes a mouse counterpart of rat L-type amino acid transporter-1, and induces system L amino acid transport in Xenopus oocytes in the presence of 4F2 heavy chain. Transfection studies in mammalian cells have indicated that the 4F2 heavy chain is expressed on the plasma membrane on its own, whereas the 4F2 light chain can be transported to the surface only in the presence of 4F2 heavy chain. 4F2 heavy chain is expressed diffusely on the surface of fibroblastic L cells, whereas it is localized selectively to the cell-cell adhesion sites in L cells expressing cadherins, These results indicate that the 4F2 heavy chain is associated covalently with an amino acid transporter and controls the cell surface expression as well as the membrane topology of the 4F2 heterodimer. Although 4F2 heavy and light chains are expressed coordinately in most tissues, the light chain is barely detected by the antibody in kidney and intestine, despite the presence of heavy chain in a complex form. The results predict the presence of multiple 4F2 light chains.