Phospholipase C is a key enzyme regulating intracellular calcium and modulating the phosphoinositide balance

Spatial and temporal activation of phosphoinositide turnover enables eukaryotic cells to perform various functions such as cell proliferation/differentiation, fertilization, neuronal functions, and cell motility. In this system, phospholipase C (PLC) is a key enzyme, which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2) into two second messengers, inositol 1,4,5-trisphosphate (Ins(1,4,5)P-3) and diacylglycerol (DAG). Ins(1,4,5)P-3 triggers the release of calcium from intracellular stores, and DAG mediates the activation of protein kinase C (PKC). In parallel, PI(4,5)P-2 also directly regulates a variety of cellular functions, including cytoskeletal remodeling, cytokinesis, phagocytosis, membrane dynamics, and channel activity, in addition to its role as a substrate for PLC and phosphatidylinositol 3-kinase (PI3K), which generates PI(3,4,5)P-3. An imbalance of these phosphoinositides contributes to the pathogeneses of various human diseases. Therefore, strict regulation of the levels of PI(4,5)P-2 and PI(3,4,5)P-3 by PLC or other interconverting enzymes is necessary for cellular functions. In this review, we focus on the roles of PLC as a calcium-regulating enzyme and as a modulator of the phosphoinositide balance. (C) 2010 Elsevier Ltd. All rights reserved.