The Actin-Binding Protein Profilin Binds to PIP 2 and Inhibits Its Hydrolysis by Phospholipase C

Profilin is generally thought to regulate actin polymerization, but the observation that acidic phospholipids dissociate the complex of profilin and actin raised the possibility that profilin might also regulate lipid metabolism. Profilin isolated from platelets binds with high affinity to small clusters of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) molecules in micelles and also in bilayers with other phospholipids. The molar ratio of the complex of profilin with PIP 2 is 1:7 in micelles of pure PIP 2 and 1:5 in bilayers composed largely of other phospholipids. Profilin competes efficiently with platelet cytosolic phosphoinositide-specific phospholipase C for interaction with the PIP 2 substrate and thereby inhibits PIP 2 hydrolysis by this enzyme. The cellular concentrations and binding characteristics of these molecules are consistent with profilin being a negative regulator of the phosphoinositide signaling pathway in addition to its established function as an inhibitor of actin polymerization.