Receptor palmitoylation and ubiquitination regulate anthrax toxin endocytosis.
Receptor palmitoylation and ubiquitination regulate anthrax toxin endocytosis.
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DOI：
10.1083/jcb.200507067
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发表时间：
2006-01-16
影响因子：
7.8
通讯作者：
van der Goot, F Gisou
中科院分区：
文献类型：
--
作者：
Abrami, Laurence;Leppla, Stephen H;van der Goot, F Gisou
炭疽毒素由三条独立的多肽链组成。只有当受体结合多肽（保护性抗原（PA））的七聚化允许两个酶亚基在胞吞作用之前结合时，才会发生成功的中毒。我们表明，这种定制的行为是由两个抵消PA受体的胞质尾的翻译后修饰。该受体是棕榈酰化的，这出乎意料地阻止了它与脂筏的结合，从而阻止了它过早的泛素化。第二种修饰由E3泛素连接酶Cbl介导，仅发生在筏中，并且是受体快速内吞所需的。因此，细胞表达棕榈酰化缺陷的突变体受体是炭疽毒素的敏感性较低，因为较低的表面受体的数量，以及过早的PA内化，而不需要七聚化。
The anthrax toxin is composed of three independent polypeptide chains. Successful intoxication only occurs when heptamerization of the receptor-binding polypeptide, the protective antigen (PA), allows binding of the two enzymatic subunits before endocytosis. We show that this tailored behavior is caused by two counteracting posttranslational modifications in the cytoplasmic tail of PA receptors. The receptor is palmitoylated, and this unexpectedly prevents its association with lipid rafts and, thus, its premature ubiquitination. This second modification, which is mediated by the E3 ubiquitin ligase Cbl, only occurs in rafts and is required for rapid endocytosis of the receptor. As a consequence, cells expressing palmitoylation-defective mutant receptors are less sensitive to anthrax toxin because of a lower number of surface receptors as well as premature internalization of PA without a requirement for heptamerization.