Toxoplasma F-Box Protein Regulation of the Apicoplast

E3泛素连接酶的SKP 1/Cullin/F-box（SCF）类是进化上的一种 一个保守的酶家族，调节包括细胞在内的关键细胞过程 循环、膜运输和信号传导。SCF-E3由四个核心组成 Rbx 1、Cullin 1、SKP 1和F-box蛋白。F-box蛋白是 亚基，其募集底物蛋白以被SCF-E3多聚泛素化，并且它们 也可以直接聚泛素化。在以前的工作中，我们发现， 弓形虫基因组包含18个预测的F盒蛋白，其中之一，TgFBLX 2， 被认为是最重要的健康因素。我们现在发现TgFBLX 2确实是 重要的寄生虫生长，并在其缺乏遗传顶质体，一个遗迹 作为重要代谢中心的质体减少。我们进一步发现， TgFBLX 2定位于独特的核仁周围区室。该项目的目标是 定义TgFBLX 2如何介导寄生虫生长。在第一个目标中，我们将确定如何 TgFBLX 2调节顶质体遗传。在第二个目标中，我们将描述 TgFBLX 2位于核仁周围区室。这些研究意义重大 因为它们将揭示细胞核和顶质体之间的新的相互作用。在 此外，这些发现可能与相关病原体有关，因为TgFBLX 2是 在疟原虫和其他顶复体中是保守的。

The SKP1/Cullin/F-box (SCF) class of E3 Ubiquitin Ligases is an evolutionarily conserved family of enzymes that regulate key cellular processes including the cell cycle, membrane trafficking, and signaling. The SCF-E3 is composed of four core components - Rbx1, Cullin1, SKP1, and a F-box protein. F-box proteins are the subunits that recruit substrate proteins to be poly-ubiquitinated by the SCF-E3, and they can also be directly poly-ubiquitinated. In previous work, we discovered that the Toxoplasma genome contains 18 predicted F-box proteins and one of these, TgFBLX2, is predicted to be the most important for fitness. We now find that TgFBLX2 is indeed important for parasite growth and in its absence inheritance of the apicoplast, a relic plastid that serves as an important metabolic hub, is reduced. We further find that TgFBLX2 localizes to a unique perinucleolar compartment. The goal of this project is to define how TgFBLX2 mediates parasite growth. In the first aim, we will determine how TgFBLX2 regulates apicoplast inheritance. In the second aim, we will characterize the perinucleolar compartment in which TgFBLX2 resides. These studies are significant because they will reveal novel interactions between the nucleus and apicoplast. In addition, these findings may be relevant to related pathogens since TgFBLX2 is conserved in Plasmodium and other apicomplexans.