死亡受体6的胞内结构域对其亚细胞定位的调节

Death Receptor 6 Subcellular Localization Regulated by Its Intracellular Domains

死亡受体6(death receptor 6,DR6)是死亡受体家族的一员,在免疫系统和神经系统中发挥着重要功能,然而,其亚细胞定位和调节机制尚不清楚。作者研究发现DR6不仅能够定位在细胞质膜表面,同时也存在于细胞内体系统。膜表面的DR6可以发生内吞,功能性单克隆抗体能够加速其内吞。通过构建一系列胞内结构域的缺失突变体,结果显示单独缺失丝氨酸/脯氨酸富集结构域,DR6在细胞膜表面定位显著增加,在内体定位显著减少。而分别缺失另外三个胞内结构域,DR6主要定位在细胞内体。以上结果提示DR6的胞内不同结构域在调控DR6的亚细胞定位和功能中发挥着重要作用。

Death receptor 6 （DR6）, a member of the death receptors, plays important roles in both immune and nervous system. However, its subcellular distribution and regulation are still not clearly defined. In this study, it was demonstrated that DR6 was located both on plasma membrane and endo/lysosomal compartment. Additionaly, functional agonist monoclonal antibody increased its endocytosis. Besides, a series of HeLa cell lines that stably express DR6 intracellular domain mutants were constructed. It was shown that deletion of DR6 intracellular serine and proline rich domain significantly decreased its intracellular Localization, while three other intracellular domain mutants mainly located on endo/lysosomal compartment. These results indicate that DR6 intracellular domains probably play important roles in regulating DR6 subcellular localization and functions.