There is evidence that the polymerization of actin takes place at the plasma membrane, and that profilactin (profilin/actin complex), the unpolymerized form of actin found in extracts of many non-muscle cells, serves as the immediate precursor. Both isolated profilin and profilactin interact with detergent when analysed by charge shift electrophoresis, indicating that they have amphipathic properties and may be able to interact directly with the plasma membrane. We demonstrate here that isolated profilin, as well as the profilactin complex, interacts with anionic phospholipids. Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) was found to be the most active phospholipid, causing a rapid and efficient dissociation of profilactin with a concomitant polymerization of the actin in appropriate conditions. These and other observations suggest the possibility of a relationship between the induction of actin filament formation and the increased activity in the phosphatidylinositol cycle seen as a result of ligand-receptor interactions in various systems.

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Profilactin, the profilin:actin complex, which is present in large amounts in extracts of many types of eukaryotic cells, appears to serve as the precursor of microfilaments. It was reported recently that profilactin interacts specifically with phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (Lassing and Lindberg: Nature 314:472-474, 1985.) The present paper describes in detail the behaviour of profilactin and profilin in the presence of different types of phospholipids and neutral lipids under different conditions. PtdIns(4,5)P2 is the only phospholipid found so far which in the presence of 80 mM KCl and at Ca2+ concentrations below 10(-5) M effectively dissociates profilactin with the resulting polymerization of the actin. Phosphatidylinositol 4-monophosphate exhibits some activity but phosphatidylinositol is inactive. Both calf spleen profilin and profilin from human platelets form stable complexes with PtdIns(4,5)P2 micelles. PtdIns(4,5)P2 is active also when incorporated together with other phospholipids in mixed vesicles.

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