Tau Protein Mediated Activation of Phospholipase C-γ Isozymes is Dependent on the presence of Arachidonic Acid

Abstract

We have previously reported tyrosine kinase-independent activation of phospholipase C (PLC)- y isozymes. The proteins that activated PLC- y 1 have been purified from bovine brain and were identified as members of the tau family of microtubule-associated proteins´, Activation of PLC- y isozymes is dependent on the composition of various lipids. The presence of unsaturated fatty acids such as arachidonic acid (AA) markedly enhances tau protein induced activation of PLC- y while saturated fatty acids being ineffective in stimulating the activation. Maximal (15- to 20-fold) activation was observed in the presence of 15 ,a M tau protein with 25 u M AA. The effect of tau and arachidonic acid induced activation was specific and most prominent for PLC- y isozymes in the presence of submicromolar concentrations of Ca2+. The effect was inhibited by the presence of phosphatidylcholine. Other polyunsaturated fatty acids, such as linoleic, linolenic, oleic and palmitoleic acids in the substrate mixture, induced similar activation but the effects were less prominent. These results suggest that, in tissues where tau protein is present, the receptors and signals that are coupled to the phospholipase A2 may activate PLC- y isozymes indirectly, without tyrosine phosphorylation, through hydrolysis of phosphatidylcholine and by generating AA, in the presence of tau protein. This process may work to amplify the signals and provide the linkage between the two different phospholipase systems.