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.