Int J Biol Sci 2020; 16(15):2761-2774. doi:10.7150/ijbs.49665 This issue
1. Philips Institute for Oral Health Research, School of Dentistry and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA
2. Department of Otolaryngology, Shanghai Pudong New Area Gongli Hospital, Shanghai, China
† These authors contributed equally to this work.
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.
Keywords: PI4, 5P2, membrane trafficking, PIPK, endosome, lysosome, autophagy