Phosphatidylinositol 4,5-bisphosphate in the Control of Membrane Trafficking

Phosphoinositides are membrane lipids generated by phosphorylation on the inositol head group of phosphatidylinositol. By specifically distributed to distinct subcellular membrane locations, different phosphoinositide species play diverse roles in modulating membrane trafficking. Among the seven known phosphoinositide species, phosphatidylinositol 4,5-bisphosphate (PI4,5P₂) is the one species most abundant at the plasma membrane. Thus, the PI4,5P₂ function in membrane trafficking is first identified in controlling plasma membrane dynamic-related events including endocytosis and exocytosis. However, recent studies indicate that PI4,5P₂ is also critical in many other membrane trafficking events such as endosomal trafficking, hydrolases sorting to lysosomes, autophagy initiation, and autophagic lysosome reformation. These findings suggest that the role of PI4,5P₂ in membrane trafficking is far beyond just plasma membrane. This review will provide a concise synopsis of how PI4,5P₂ functions in multiple membrane trafficking events. PI4,5P₂, the enzymes responsible for PI4,5P₂ production at specific subcellular locations, and distinct PI4,5P₂ effector proteins compose a regulation network to control the specific membrane trafficking events.