Duprez V, Smoljanovic M, Lieb M, Dautry-Varsat A
Unité de Biologie des Interactions Cellulaires, CNRS URA 361, Institut Pasteur, Paris, France.
J Cell Sci. 1994 May;107 ( Pt 5):1289-95. doi: 10.1242/jcs.107.5.1289.
The T lymphocyte growth factor interleukin 2 binds to surface high-affinity receptors and is rapidly internalized and degraded in acidic organelles. The alpha and beta chains of high-affinity interleukin 2 receptors are internalized together with interleukin 2. To identify the intracellular pathway followed by interleukin 2, we have compared the subcellular distribution of interleukin 2, transferrin and a fluid-phase marker, horseradish peroxidase, in the human T cell line IARC 301.5. Transferrin was used as a marker of early and recycling endosomes, and horseradish peroxidase to probe for the whole endocytic pathway. Fractionation of intracellular organelles on a discontinuous sucrose gradient showed that internalized interleukin 2 is initially mostly found in compartments with similar densities to transferrin, e.g. early and recycling endosomes. The kinetics of entry and exit of interleukin 2 from such organelles was much slower than that of transferrin. Later on, interleukin 2 is predominantly found in dense lysosome-containing fractions. Very little, if any, interleukin 2 was found in fractions corresponding to late endosomes containing horseradish peroxidase. These results suggest that, after endocytosis, interleukin 2 enters early or recycling endosomes before it reaches dense lysosomes.
T淋巴细胞生长因子白细胞介素2与表面高亲和力受体结合，迅速内化并在酸性细胞器中降解。高亲和力白细胞介素2受体的α链和β链与白细胞介素2一起内化。为了确定白细胞介素2所遵循的细胞内途径，我们比较了白细胞介素2、转铁蛋白和一种液相标记物辣根过氧化物酶在人T细胞系IARC 301.5中的亚细胞分布。转铁蛋白用作早期和循环内体的标记物，辣根过氧化物酶用于探测整个内吞途径。通过在不连续蔗糖梯度上对细胞内细胞器进行分级分离，结果显示内化的白细胞介素2最初大多存在于与转铁蛋白密度相似的区室中，例如早期和循环内体。白细胞介素2进出此类细胞器的动力学比转铁蛋白慢得多。随后，白细胞介素2主要存在于含有致密溶酶体的组分中。在对应于含有辣根过氧化物酶的晚期内体的组分中，几乎没有发现白细胞介素2（如果有的话）。这些结果表明，内吞作用后，白细胞介素2在到达致密溶酶体之前先进入早期或循环内体。
