PI4P

PI4P, or phosphatidylinositol 4-phosphate, is a phosphatidylinositol phosphate in eukaryotic membranes. It contains a single phosphate group on the 4-position of the inositol head group and functions as both a lipid intermediate and a signaling molecule that helps define membrane identity and trafficking routes.

Synthesis of PI4P is carried out by phosphatidylinositol 4-kinases (PI4Ks) that phosphorylate PI at the 4-position. In mammals, two main classes exist: type II kinases (PI4K2A and PI4K2B) and type III kinases (PI4KA and PI4KB). These enzymes have distinct subcellular localizations, with PI4KA often found at the plasma membrane and early secretory compartments and PI4KB predominantly associated with the Golgi, while PI4K2 enzymes localize to endosomal and Golgi membranes. PI4P generated at various locations serves as a platform for specific protein interactions and lipid signaling.

Functions of PI4P include serving as a precursor for the synthesis of PI(4,5)P2 via PI4P 5-kinases, and acting as a docking site for effector proteins that recognize PI4P through lipid-binding domains. This enables recruitment of trafficking factors, lipid transfer proteins, and enzymes involved in membrane budding, fusion, and lipid exchange. PI4P also participates in coordinating lipid composition and membrane trafficking at the Golgi and at membrane contact sites between the endoplasmic reticulum and other organelles, contributing to organelle identity and proper vesicle routing.

Turnover of PI4P is tightly controlled by phosphatases such as Sac1, which dephosphorylates PI4P back to phosphatidylinositol, and other lipid phosphatases that regulate PI4P pools. In yeast, the balance of PI4P is maintained by kinases like Stt4 and Pik1 and the Sac1 phosphatase, illustrating the cycle that governs PI4P-dependent processes across membranes.