Phosphoinositides in phagosome-lysosome-enzyme secretion network

Phosphoinositides have emerged as important regulators of membrane and protein trafficking in mammalian cells. Examples include, but are not limited to, phagosomal/endosomal trafficking, regulated exocytosis and delivery of proteins to vacuole/lysosome. A model organism for unraveling new functions for phosphoinositides has been the yeast S. cerevisiae; yet, several mammalian-type pathways are not present in yeast.

An alternative simple model is the ciliate Tetrahymena which possesses three well-characterized membrane trafficking pathways: regulated exocytosis of dense-core vesicles, constitutive secretion of lysosomal enzymes and phagocytosis. The latter two pathways are connected through lysosomes which either fuse to the plasma membrane and release their content to the extracellular space or fuse to maturing phagosomes, resulting in the formation of phagolysosomes.We have shown that PtdIns3P, PtdIns4P, PtdIns3,5P2 and PtdIns4,5P2 are present in T. thermophila. By studying wild-type and phagocytosis and secretion mutant strains we propose that all four phosphoinositides are involved in lysosomal homeostasis, albeit at different stages of the phagocytosis → secretion network. Proper regulation of PtdIns4,5P2 levels by PI-PLC is crucial for the initiation of phagocytosis. D-3 phosphoinositides regulate enzyme secretion at the level of phagolysosome. Also, the presence of a lysosomal secretion-sensitive pool of PtdIns4P suggests that PtdIns4P turnover is linked to enzyme secretion. The use of GFP-PH/FYVE domains will further elucidate their localization and dynamics in live cells during induction of phagocytosis and secretion.

Speaker: D. Galanopoulou
Associate Professor, Department of Chemistry, University of Athens
Time: Monday, 6 April 2009, 13:00