PI3P

Phosphatidylinositol 3-phosphate (PI3P) is a phosphoinositide formed by phosphorylation of phosphatidylinositol at the 3-position of the inositol ring. It is enriched on endosomal membranes, particularly early endosomes and on membranes associated with autophagy, and serves as a lipid beacon for PI3P-binding effector proteins.

Biosynthesis and turnover: PI3P is produced principally by class III phosphatidylinositol 3-kinase (VPS34) in a complex with Beclin-1 and the regulatory subunit VPS15; in autophagy, a complex containing Beclin-1 and ATG14L directs PI3P production on pre-autophagosomal structures. PI3P is generated on endosomal and autophagic membranes and is dephosphorylated by myotubularin family phosphatases to regenerate PI. The level of PI3P is also dynamically regulated by the PIKfyve kinase that converts PI3P to PI(3,5)P2 on endosomes.

Functions: PI3P recruits effector proteins containing FYVE or PX domains, such as EEA1 and Hrs, enabling endosomal tethering, trafficking, and maturation, as well as ESCRT-mediated sorting. In autophagy, PI3P helps recruit ATG proteins (e.g., WIPI2) to promote phagophore expansion and autophagosome formation. Due to its distinct localization, PI3P serves as a useful marker for early endosomal and autophagic membranes in imaging studies.