Otero Carolina, Groettrup Marcus, Legler Daniel F
Biotechnology Institute Thurgau, University of Konstanz, Konstanzerstrasse 19, CH-8274 Tägerwilen, Switzerland.
J Immunol. 2006 Aug 15;177(4):2314-23. doi: 10.4049/jimmunol.177.4.2314.
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.
趋化因子受体CCR7及其配体CCL19和CCL21对于淋巴细胞和树突状细胞归巢至二级淋巴组织起着关键作用。然而，CCR7如何感知趋化因子梯度以及迁移如何终止仍知之甚少。在本研究中，我们证明CCR7(-GFP)在与CCL19结合后会被内吞至含有转铁蛋白受体的早期内体中，但在CCL21触发时内吞较少。CCR7的内化不依赖于脂筏，但依赖于发动蛋白和Eps15，并受到高渗蔗糖的抑制，提示为网格蛋白依赖的内吞作用。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。相反，内化的CCL19被分选至溶酶体进行降解，显示出内化的CCR7及其配体的相反命运。
