Investigating the Phosphatidylinositol-4-Phosphate Signaling and the Phosphoinositide Sec14-Like PITP-Dependent Regulation in the Apicomplexa Parasite Toxoplasma gondii

Abstract

Phosphoinositides (PIPs) are a biologically essential class of phospholipids that contribute to organelle membrane identity, modulate membrane trafficking pathways, and are central components of major signal transduction pathways that operate on the cytosolic face of intracellular membranes in eukaryotes. Apicomplexans are obligate intracellular parasites that are important causative agents of disease in animals and humans and are experimentally tractable models for studying the deepest rooted common eukaryotic ancestor. As such, these organisms offer insights into the evolutionary origins of essential PIP signaling pathways. Herein, in this work it is reviewed and discussed the regulatory mechanisms that control the spatial and temporal regulation of PIP in the Apicomplexan parasites Plasmodium and T. gondii when compared with current eukaryotic models. Then, phosphatidylinositol-4-phosphate (PtdIns4P) –an essential potentiator of exocytic trafficking from the trans-Golgi network (TGN) to the plasma membrane in yeast and mammalian cells – is characterized in intracellular tachyzoites of T. gondii. PtdIns4P pools were detected in the Golgi/TGN and post TGN compartments and through high resolution imaging techniques it was confirmed that PtdIns4P regulates the formation of mature dense granules (DG). Contrary to current models, this finding indicated that the process of DG biogenesis is a multistep process that resembles those characterized for regulated secretory pathways in professional secretory cells. In addition, the description of the cohort of T. gondii Sec14-like PITPs led to the characterization of a candidate with potential sterol precursor-binding and transport to the parasite. Our data demonstrated that studying PIP signaling and Sec14-like PITPs-dependent regulation in Apicomplexa organisms offers crucial insight into the evolutionary origins of essential PIP signaling pathways.