Mangasarian A, Foti M, Aiken C, Chin D, Carpentier J L, Trono D
Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Immunity. 1997 Jan;6(1):67-77. doi: 10.1016/s1074-7613(00)80243-5.
The HIV Nef protein down-regulates the cell surface expression of CD4 and of MHC I at least in part through accelerated endocytosis. To investigate further the mechanism of this effect, we created chimeric integral membrane proteins comprising the extracellular and transmembrane regions of CD4 or CD8 and Nef as the cytoplasmic domain. These fusion molecules could down-modulate CD4 in trans in a dileucine-dependent manner. Furthermore, in spite of lacking receptor-derived internalization signals, the Nef-containing chimeras underwent both Golgi retention and rapid endocytosis via clathrin-coated pits. Taken together, these data suggest that Nef down-regulates CD4 and probably MHC I by physically connecting these receptors with sorting pathways in the Golgi and at the plasma membrane.
HIV Nef蛋白至少部分通过加速内吞作用下调CD4和MHC I的细胞表面表达。为了进一步研究这种作用的机制，我们构建了嵌合整合膜蛋白，其包含CD4或CD8的细胞外和跨膜区域以及作为细胞质结构域的Nef。这些融合分子能够以依赖双亮氨酸的方式反式下调CD4。此外，尽管缺乏受体衍生的内化信号，但含Nef的嵌合体通过网格蛋白包被小窝经历了高尔基体滞留和快速内吞作用。综上所述，这些数据表明Nef通过将这些受体与高尔基体和质膜中的分选途径物理连接来下调CD4以及可能下调MHC I。
