Toxoplasma F-Box Protein Regulation of the Apicoplast

点击翻译按钮获取中文摘要

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.