Gangliosides that associate with lipid rafts mediate transport of cholera and related toxins from the plasma membrane to endoplasmic reticulm
Gangliosides that associate with lipid rafts mediate transport of cholera and related toxins from the plasma membrane to endoplasmic reticulm
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DOI：
10.1091/mbc.e03-06-0354
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发表时间：
2003-12-01
影响因子：
3.3
通讯作者：
Lencer, WI
中科院分区：
文献类型：
--
作者：
Fujinaga, Y;Wolf, AA;Lencer, WI
霍乱毒素（CT）从肠细胞的质膜进入内质网（ER），在内质网中A亚单位的一部分，即A1链，穿过膜进入胞质溶胶引起疾病。一种相关的毒素，LTIIb，与肠细胞结合，但不会引起毒性。在这里，我们表明，CT的B-亚基作为一个载体的A-亚基的ER发生解体。B亚单位与脂筏中的神经节苷脂结合，并与神经节苷脂一起进入ER。在许多细胞中，LTIIb遵循类似的途径，但在人肠细胞中，它与神经节苷脂结合，而神经节苷脂不能与脂筏结合，并且它被从逆行途径分选到ER。我们的研究结果解释了为什么LTIIb在人类中不引起疾病，并表明对脂筏具有高亲和力的神经节苷脂可能为毒素转运到ER提供了一种通用的载体。
Cholera toxin (CT) travels from the plasma membrane of intestinal cells to the endoplasmic reticulum (ER) where a portion of the A-subunit, the A1 chain, crosses the membrane into the cytosol to cause disease. A related toxin, LTIIb, binds to intestinal cells but does not cause toxicity. Here, we show that the B-subunit of CT serves as a carrier for the A-subunit to the ER where disassembly occurs. The B-subunit binds to gangliosides in lipid rafts and travels with the ganglioside to the ER. In many cells, LTIIb follows a similar pathway, but in human intestinal cells it binds to a ganglioside that fails to associate with lipid rafts and it is sorted away from the retrograde pathway to the ER. Our results explain why LTIIb does not cause disease in humans and suggest that gangliosides with high affinity for lipid rafts may provide a general vehicle for the transport of toxins to the ER.