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首页> 外文期刊>Journal of Cell Science >Shiga toxin stimulates clathrin-independent endocytosis of the VAMP2, VAMP3 and VAMP8 SNARE proteins
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Shiga toxin stimulates clathrin-independent endocytosis of the VAMP2, VAMP3 and VAMP8 SNARE proteins

机译：志贺毒素刺激VAMP2，VAMP3和VAMP8 SNARE蛋白的网格蛋白非依赖性内吞作用

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摘要

Endocytosis is an essential cellular process that is often hijacked by pathogens and pathogenic products. Endocytic processes can be classified into two broad categories, those that are dependent on clathrin and those that are not. The SNARE proteins VAMP2, VAMP3 and VAMP8 are internalized in a clathrin-dependent manner. However, the full scope of their endocytic behavior has not yet been elucidated. Here, we found that VAMP2, VAMP3 and VAMP8 are localized on plasma membrane invaginations and very early uptake structures that are induced by the bacterial Shiga toxin, which enters cells by clathrin-independent endocytosis. We show that toxin trafficking into cells and cell intoxication rely on these SNARE proteins. Of note, the cellular uptake of VAMP3 is increased in the presence of Shiga toxin, even when clathrin-dependent endocytosis is blocked. We therefore conclude that VAMP2, VAMP3 and VAMP8 are removed from the plasma membrane by non-clathrin-mediated pathways, in addition to by clathrin-dependent uptake. Moreover, our study identifies these SNARE proteins as the first transmembrane trafficking factors that functionally associate at the plasma membrane with the toxin-driven clathrin-independent invaginations during the uptake process.
机译：胞吞作用是必不可少的细胞过程，经常被病原体和病原体产物劫持。内吞过程可分为两大类，一类依赖网格蛋白，一类不依赖网格蛋白。 SNARE蛋白VAMP2，VAMP3和VAMP8以网格蛋白依赖性方式内化。但是，尚未阐明其胞吞行为的全部范围。在这里，我们发现VAMP2，VAMP3和VAMP8定位于质膜的内陷和细菌志贺毒素诱导的非常早的摄取结构中，后者通过网格蛋白非依赖性内吞作用进入细胞。我们表明毒素贩运到细胞和细胞中毒依赖于这些SNARE蛋白。值得注意的是，即使阻断了网格蛋白依赖性内吞作用，在志贺毒素存在下，VAMP3的细胞摄取也会增加。因此，我们得出结论，除网格蛋白依赖性摄取外，还通过非clathrin介导的途径从质膜上除去了VAMP2，VAMP3和VAMP8。此外，我们的研究确定这些SNARE蛋白是首个跨膜运输因子，在摄取过程中在质膜上与毒素驱动的网格蛋白非依赖性内吞功能相关联。

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