Fang Yi, Wu Ning, Gan Xin, Yan Wanhua, Morrell James C, Gould Stephen J
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
PLoS Biol. 2007 Jun;5(6):e158. doi: 10.1371/journal.pbio.0050158.
Exosomes are secreted organelles that have the same topology as the cell and bud outward (outward is defined as away from the cytoplasm) from endosome membranes or endosome-like domains of plasma membrane. Here we describe an exosomal protein-sorting pathway in Jurkat T cells that selects cargo proteins on the basis of both higher-order oligomerization (the oligomerization of oligomers) and plasma membrane association, acts on proteins seemingly without regard to their function, sequence, topology, or mechanism of membrane association, and appears to operate independently of class E vacuolar protein-sorting (VPS) function. We also show that higher-order oligomerization is sufficient to target plasma membrane proteins to HIV virus-like particles, that diverse Gag proteins possess exosomal-sorting information, and that higher-order oligomerization is a primary determinant of HIV Gag budding/exosomal sorting. In addition, we provide evidence that both the HIV late domain and class E VPS function promote HIV budding by unexpectedly complex, seemingly indirect mechanisms. These results support the hypothesis that HIV and other retroviruses are generated by a normal, nonviral pathway of exosome biogenesis.
外泌体是分泌性细胞器，其拓扑结构与细胞相同，从内体膜或质膜的内体样结构域向外出芽（向外定义为远离细胞质）。在此，我们描述了Jurkat T细胞中的一种外泌体蛋白质分选途径，该途径基于高阶寡聚化（寡聚物的寡聚化）和质膜结合来选择货物蛋白，作用于蛋白质时似乎不考虑其功能、序列、拓扑结构或膜结合机制，并且似乎独立于E类液泡蛋白分选（VPS）功能运行。我们还表明，高阶寡聚化足以将质膜蛋白靶向HIV病毒样颗粒，多种Gag蛋白具有外泌体分选信息，并且高阶寡聚化是HIV Gag出芽/外泌体分选的主要决定因素。此外，我们提供证据表明，HIV晚期结构域和E类VPS功能通过出人意料的复杂、看似间接的机制促进HIV出芽。这些结果支持了HIV和其他逆转录病毒是通过外泌体生物发生的正常、非病毒途径产生的这一假说。
