Abstract
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.