Phosphatidylinositol-4-phosphate signaling regulates dense granule biogenesis and exocytosis in Toxoplasma gondii

Abstract

Phosphoinositide metabolism defines the foundation of a major signaling pathway that is conserved throughout the eukaryotic kingdom. The 4-OH phosphorylated phosphoinositides such as phosphatidylinositol-4-phosphate (PtdIns4P) and phosphatidylinositol-4,5-bisphosphate are particularly important molecules as these execute intrinsically essential activities required for the viability of all eukaryotic cells studied thus far. Using intracellular tachyzoites of the apicomplexan parasite Toxoplasma gondii as model for assessing primordial roles for PtdIns4P signaling, we demonstrate the presence of PtdIns4P pools in Golgi/trans-Golgi (TGN) system and in post-TGN compartments of the parasite. Moreover, we show that deficits in PtdIns4P signaling result in structural perturbation of compartments that house dense granule cargo with accompanying deficits in dense granule exocytosis. Taken together, the data report a direct role for PtdIns4P in dense granule biogenesis and exocytosis. The data further indicate that the biogenic pathway for secretion-competent dense granule formation in T. gondii is more complex than simple budding of fully matured dense granules from the TGN.