The Plastid of Toxoplasma gondii

弓形虫是一种重要的条件致病菌， 全球艾滋病患者寄生虫拥有一个独特的和必要的细胞器称为顶质体， 它在遗传和功能上都与叶绿体有关。因为人类宿主缺乏一种类似的 细胞器，顶质体是开发抗寄生虫药物的重要潜在靶点。小 已知这种细胞器的生物起源，它由四层膜包围。到目前为止，只有 已经探索了对顶质体腔的靶向。这些蛋白质被一个信号所靶向 允许进入分泌系统的序列和将它们从ER路由的转运肽 到质体。我们已经提出了挑衅性的证据表明，后一步发生在一个高尔基独立 方式在过去的研究期间，我们鉴定了两种顶质体膜蛋白（a 转运蛋白和蛋白酶），两者都缺乏典型的靶向序列。与Luminal相比， 蛋白质，这些蛋白质显示细胞周期依赖性定位于顶质体。因为这些 差异以及不同的最终目的地，介导靶向的途径和序列 非管腔蛋白质的合成可能涉及新的元件。该提案概述了旨在 表征了一组定位于各种顶质体隔室的蛋白质，并将解剖 机制和序列对这些蛋白质的正确定位很重要。我们还将 确定顶质体膜蛋白的靶向是否由已知的 参与内质网出口过程或内质网到高尔基体的运输。这些研究将扩大我们对 这一独特的细胞器的生物发生，并提供有关其功能的额外信息。

Toxoplasma gondii is an important opportunistic pathogen, affecting up to one‐third of untreated AIDS patients worldwide. The parasite possesses a unique and essential organelle called the apicoplast, which is genetically and functionally related to chloroplasts. Because the human host lacks a similar organelle, the apicoplast is an important potential target for development of anti‐parasitic agents. Little is known about the biogenesis of this organelle, which is bounded by four membranes. Until now, only targeting to the apicoplast lumen has been explored. Such proteins are targeted courtesy of a signal sequence that allows entry into the secretory system and a transit peptide that routes them from the ER to the plastid. We have presented provocative evidence that the latter step occurs in a Golgiindependent manner. In the past grant period we identified two apicoplast membrane proteins (a transporter and a protease), both of which lack canonical targeting sequences. In contrast to luminal proteins, these proteins show cell cycle dependent localization to the apicoplast. Because of these differences as well as the distinct ultimate destinations, the routes and sequences that mediate targeting of non‐luminal proteins likely involve novel elements. This proposal outlines experiments aimed at characterizing a set of proteins localized to various apicoplast compartments, and will dissect the mechanisms and sequences important for the proper localization of these proteins. We will also determine whether targeting of apicoplast membrane proteins is assisted by molecules known to be involved in ER exit processes or ER to Golgi trafficking. These studies will expand our understanding of the biogenesis of this unique organelle and provide additional information concerning its function.