Opposite fate of endocytosed CCR7 and its ligands: Recycling versus degradation
Opposite fate of endocytosed CCR7 and its ligands: Recycling versus degradation
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DOI：
10.4049/jimmunol.177.4.2314
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发表时间：
2006-08-15
影响因子：
4.4
通讯作者：
Legler, Daniel F.
中科院分区：
文献类型：
--
作者：
Otero, Carolina;Groettrup, Marcus;Legler, Daniel F.
趋化因子受体CCR7及其配体CCL19和CCL21在淋巴细胞和树突状细胞向次级淋巴组织的归巢中起着至关重要的作用。然而，CCR7如何感知趋化因子的梯度以及迁移是如何终止的，人们知之甚少。在本研究中，我们证明CCR7（-GFP）在CCL19结合时被内吞入含有转铁蛋白受体的早期核内体，但在CCL21触发时则较少。CCR7的内化不依赖于脂筏，但依赖于动力蛋白和Eps15，并被高渗透性蔗糖抑制，表明其内化依赖于网格蛋白。趋化因子去除后，内化的CCR7循环回到质膜，并能够再次介导迁移。相比之下，内化的CCL19被分类到溶酶体中降解，内吞的CCR7及其配体表现出相反的命运。
The chemokine receptor CCR7 and its ligands CCL19 and CCL21 play a crucial role for the homing of lymphocytes and dendritic cells to secondary lymphoid tissues. Nevertheless, how CCR7 senses the gradient of chemokines and how migration is terminated are poorly understood. In this study, we demonstrate that CCR7(-GFP) is endocytosed into early endosomes containing transferrin receptor upon CCL19 binding, but less upon CCL21 triggering. Internalization of CCR7 was independent of lipid rafts but relied on dynamin and Eps15 and was inhibited by hypertonic sucrose, suggesting clathrin-dependent endocytosis. After chemokine removal, internalized CCR7 recycled back to the plasma membrane and was able to mediate migration again. In contrast, internalized CCL19 was sorted to lysosomes for degradation, showing opposite fate for endocytosed CCR7 and its ligand.