Abstract

AbstractPhosphoinositides are phospholipids that contain a phosphorylated inositol head group. The position and number of phosphate groups varies, which results in seven phosphoinositide species. A large family of enzymes have evolved to specifically modify phosphoinositides.Phosphoinositide kinasesandphosphatasesmodify the phosphorylation state of the inositol head group, whereas phospholipases hydrolyse phosphoinositides to release the soluble head group into the cytosol. The combined action of these enzymes produces the phosphoinositide signature of a cell, where certain membrane compartments are enriched or depleted of specific phosphoinositides. The cellular response of a certain phosphoinositide signature is mediated by phosphoinositide effectors. These effectors contain phosphoinositide recognition domains, which guide the effector to the appropriate location and in many cases also modulate their activity. Phosphoinositides play crucial roles in many cellular processes, including cell signalling, cytoskeletal rearrangements, vesicle transport and control of ion channels.Key Concepts:Phosphoinositides are phospholipids that contain a negatively charged phosphoinositol head group.Phosphoinositides are modified by phosphoinositide kinases, phosphatases and phospholipases.Specific phosphoinositides are enriched in different membrane compartments.Specific phosphoinositide recognition modules are linked to effectors.Tight regulation of generation and depletion of phosphoinositides allows spatio‐temporal control of complex cellular processes.PI3KI and PTEN, which control PtdIns(3,4,5)P3levels, belong to the most frequently mutated genes in cancer.

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