INHIBITION OF PHOSPHOLIPASE-D ACTIVITY BY FODRIN - AN ACTIVE-ROLE FORTHE CYTOSKELETON

Phospholipase D (PLD) is a major enzyme implicated in important cellul ar processes such as secretion and proliferation. The knowledge of its regulation is essential to understand the control of these phenomena. Several proteins activating PLD have been described in the last years . In this report, we chromatographed bovine brain cytosolic proteins t o identify fodrin, the nonerythroid spectrin, as the first described i nhibitor of PLD. A cytosolic fraction with an inhibitory effect on PLD activity loses its capacity after immunoprecipitation of fodrin. More over, at 1 nM, purified fodrin blocks fully and quickly PLD activity, whatever the stimuli used. In contrast, fodrin has no effect on adenyl ate cyclase activity. Fodrin-analogous proteins like dimeric or tetram eric erythroid spectrin have the same inhibitory effect on PLD, at hig her concentrations. Other cytoskeletal proteins, actin and vimentin, a re inefficient on PLD inhibition. The mechanisms implicated in PLD mod ulation such as post-translational modifications of fodrin and the rol e of small G-proteins on the cytoskeleton regulation are discussed. In conclusion, this study reveals that fodrin is involved in the control of PLD activity, suggesting that the cytoskeleton could have an activ e role in control of secretion and proliferation.