phosphoinositide

Phosphoinositides are a group of phosphorylated derivatives of phosphatidylinositol, a phospholipid component of cell membranes. They are produced by adding phosphate groups to the inositol head group at various positions (3, 4 and 5). Although they represent a small fraction of total membrane lipids, these molecules function as key signaling lipids and as determinants of membrane identity, recruiting specific effector proteins to membranes.

The best-characterized species include PI(4)P, PI(4,5)P2 and PI(3,4,5)P3, with distinct cellular localizations and roles. PI(4)P is enriched in the Golgi and plasma membrane, PI(4,5)P2 is abundant at the inner leaflet of the plasma membrane, and PI(3,4,5)P3 is rapidly produced after growth factor stimulation and acts in many signaling cascades.

Biosynthesis and turnover: PI4 kinases generate PI(4)P; PI(4)P can be converted to PI(4,5)P2 by PIP5 kinases; PI3-kinases generate PI(3,4,5)P3 from PI(4,5)P2. Lipid phosphatases such as PTEN and INPP5 family remove phosphates to terminate signals; phospholipase C hydrolyzes PI(4,5)P2 to generate DAG and IP3, linking to calcium signaling.

Functions: They regulate vesicle trafficking, cytoskeletal organization, ion channels, endocytosis, exocytosis, and receptor signaling by serving as docking sites for proteins with PH, PX or ENTH domains.

Clinical relevance: Dysregulation of phosphoinositide signaling has been linked to cancer, metabolic disorders, neurodegenerative diseases, and inherited disorders of membrane trafficking.