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Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.

Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane compartments imparts “surface identity” to the cell membrane. The phosphorylated heads of PIPs are recognized and bound by particular proteins, including proteins that help in vesicle coat assembly.

For example, the cytosolic side of the plasma membrane has high concentrations of the PI(4,5)P2, which helps recruit proteins such as dynamin and AP2 for clathrin-mediated endocytosis. PI(4,5)P2 is rapidly formed and destroyed by localized enzymes at particular locations and at specific times. This helps control the precise timing of clathrin-coated vesicle formation. Once the coated vesicle pinches off the plasma membrane during endocytosis, PI(4,5)P2 is destroyed from the site.

Many such PIs are involved in the secretory or endocytic pathways, such as PI(3)P localized at early endosomes and intraluminal vesicles of late endosomes, PI(4)P localized at the TGN, secretory granules, and synaptic vesicles; and PI(3,5)P2 localized at the late endosome boundary membrane.

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