Genetic Evidence that an Endosymbiont-derived Endoplasmic Reticulum-associated Protein Degradation (ERAD) System Functions in Import of Apicoplast Proteins
Genetic Evidence that an Endosymbiont-derived Endoplasmic Reticulum-associated Protein Degradation (ERAD) System Functions in Import of Apicoplast Proteins
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DOI：
10.1074/jbc.m109.044024
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发表时间：
2009-11-27
影响因子：
4.8
通讯作者：
Striepen, Boris
中科院分区：
文献类型：
--
作者：
Agrawal, Swati;van Dooren, Giel G.;Striepen, Boris
大多数顶复合体寄生物都有一个残叶绿体，即顶质体，这对它们的生存至关重要。顶质体的基因组很小，但其大部分蛋白质是核编码的，并输入到细胞器中。已经提出了几个模型来解释蛋白质如何穿过围绕着顶质体的四层膜；然而，鉴别这些模型的实验数据在很大程度上缺失。在这里，我们提出的遗传证据表明，顶质体蛋白的进口取决于源自内质网相关蛋白降解（ERAD）系统的元件。我们在刚地弓形虫中发现了两组ERAD成分，一组与内质网和细胞质有关，另一组定位于顶质体的膜。我们在顶质体Der1（假定的顶质体ERAD复合体的孔）中设计了一个条件零突变体，发现Der1（Ap）的缺失导致了顶质体蛋白输入的缺失和随后的寄生虫死亡。
Most apicomplexan parasites harbor a relict chloroplast, the apicoplast, that is critical for their survival. Whereas the apicoplast maintains a small genome, the bulk of its proteins are nuclear encoded and imported into the organelle. Several models have been proposed to explain how proteins might cross the four membranes that surround the apicoplast; however, experimental data discriminating these models are largely missing. Here we present genetic evidence that apicoplast protein import depends on elements derived from the ER-associated protein degradation (ERAD) system of the endosymbiont. We identified two sets of ERAD components in Toxoplasma gondii, one associated with the ER and cytoplasm and one localized to the membranes of the apicoplast. We engineered a conditional null mutant in apicoplast Der1, the putative pore of the apicoplast ERAD complex, and found that loss of Der1(Ap) results in loss of apicoplast protein import and subsequent death of the parasite.