Toxoplasma F-Box Protein Regulation of the Apicoplast

E3泛素连接酶的Skp1/cullin/F-box(SCF)类在进化上是一种 保守的酶家族，调节包括细胞在内的关键细胞过程 周期、膜运输和信号转导。SCF-E3由四个核心组成 组分-Rbx1、Cullin1、Skp1和一个F-box蛋白。F-box蛋白是 招募底物蛋白的亚基被SCF-E3多泛素化，它们 也可以直接被多泛素化。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-box蛋白，其中之一TgFBLX2， 被预测是对健康最重要的。我们现在发现TgFBLX2确实是 对寄生虫的生长很重要，在它不存在的情况下，顶生质体是一种遗迹 作为重要新陈代谢枢纽的叶绿体减少。我们进一步发现， TgFBLX2定位于一个独特的核周室。这个项目的目标是 定义TgFBLX2如何调节寄生虫的生长。在第一个目标中，我们将确定 TgFBLX2调控质外体遗传。在第二个目标中，我们将描述 TgFBLX2所在的核周室。这些研究具有重要意义 因为它们将揭示细胞核和质外体之间的新的相互作用。在……里面 此外，这些发现可能与相关病原体有关，因为TgFBLX2是 在疟原虫和其他顶端复合体中保守。

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.