Phosphatidylinositol 4,5‐bisphosphate: Targeted production and signaling

Phosphatidylinositol 4,5‐bisphosphate (PI4,5P 2 ) is a key lipid signaling molecule that regulates a vast array of biological activities. PI4,5P 2 can act directly as a messenger or can be utilized as a precursor to generate other messengers: inositol trisphosphate, diacylglycerol, or phosphatidylinositol 3,4,5‐trisphosphate. PI4,5P 2 interacts with hundreds of different effector proteins. The enormous diversity of PI4,5P 2 effector proteins and the spatio‐temporal control of PI4,5P 2 generation allow PI4,5P 2 signaling to control a broad spectrum of cellular functions. PI4,5P 2 is synthesized by phosphatidylinositol phosphate kinases (PIPKs). The array of PIPKs in cells enables their targeting to specific subcellular compartments through interactions with targeting factors that are often PI4,5P 2 effectors. These interactions are a mechanism to define spatial and temporal PI4,5P 2 synthesis and the specificity of PI4,5P 2 signaling. In turn, the regulation of PI4,5P 2 effectors at specific cellular compartments has implications for understanding how PI4,5P 2 controls cellular processes and its role in diseases.