Regulation of inositol lipid-specific phospholipase C delta by changes in Ca2+ ion concentrations

Studies of inositol lipid-specific phospholipase C (PLC) have elucidated the main regulatory pathways for PLC beta and PLC gamma but the regulation of PLC delta isoenzymes still remains obscure. Here we demonstrate that an increase in Ca2+ ion concentration within the physiological range (0.1-10 mu M) is sufficient to stimulate PLC delta 1, but not PLC gamma 1 and PLC beta 1, to hydrolyse cellular inositol lipids present in permeabilized cells. The activity of PLC delta 1 is further enhanced in the presence of phosphatidylinositol transfer protein (PI-TP). Both full activation by Ca2+ ions and stimulation in the presence of PI-TP require an intact PH domain involved in the membrane attachment of PLC delta 1. The physiological implication of this study is that PLC delta 1 could correspond to a previously uncharacterized PLC responsible for Ca2+ ion-stimulated inositol lipid hydrolysis observed in many cellular systems.