Figure 1. Phosphatidylinositol(4,5)bisphosphate (PI(4,5)P₂).

(A) Multiple functions of PI(4,5)P₂ at the plasma membrane. PI(4,5)P₂ is a substrate for two signalling pathways, phospholipase C (PLC) and phosphoinositide 3-kinase (PI3K). PI(4,5)P₂ also functions as an intact lipid to regulate ion channels, membrane dynamics and the actin cytoskeleton. Three pathways can deplete PI(4,5)P₂ levels, marked with yellow arrows – PLC, PI3K and 5-phosphatase. Abbreviations: DAG, diacylglycerol; GPCR, G-protein coupled receptor; IP₃, inositol(1,4,5)trisphosphate; PI, phosphatidylinositol; PI4K, PI 4-kinase; PI4P, phosphatidylinositol 4-phosphate; PI4P5K, PI4P 5-kinase; PKC, protein kinase C; RTK, receptor tyrosine kinase. (B) Structure of PI(4,5)P₂. PI(4,5)P₂ comprises a glycerol backbone with an inositol headgroup which is phosphorylated at the 4 and 5 positions on the inositol ring. The fatty acid composition of PI(4,5)P₂ is distinctive; stearic acid (C18:0) at the sn-1 position and arachidonic acid (C20:4) at the sn-2 position of the glycerol backbone. (C) PI(4,5)P₂ can bind domains such as PH or by electrostatic interactions to basic residues of arginines and lysines. PI(4,5)P₂ can bind to structured domains such as PH domains or it can bind to unstructured clusters of positively charged lysine and arginine residues in proteins due to electrostatic interactions. Abbreviation: PH domain, pleckstrin homology domain.