Requirement of phosphatidylinositol 4,5-bisphosphate for α-actinin function

Abstract

INOSITOL phospholipid turnover is enhanced during mitogenic stimulation of cells by growth factors¹ and the breakdown of phosphatidylinositol 4,5-bisphosphate (PtdInsP₂) may be important in triggering cell proliferation. PtdInsP₂ also binds actin-binding proteins to regulate their activity^2–7, but it is not yet understood how this control is achieved. The protein α-actinin from striated muscle contains large amounts of endogenous PtdInsP₂, whereas that from smooth muscle has only a little but will bind exogenously added PtdInsP₂. In vitro α-actinin binds to F-actin and will crosslink actin filaments, increasing the viscosity of F-actin solutions^8,9. We report here that α-actinin from striated muscle is an endogenous PtdInsP₂-bound protein and that the specific interaction between α-actinin and PtdInsP₂ regulates the F-actin-gelating activity of α-actinin. Although the F-actin-gelating activity of α-actinin from smooth muscle is much reduced compared with that from striated muscle, exogenous PtdInsP₂ can enhance the activity of smooth muscle α-actinin to the level seen in striated muscles. These results show that PtdInsP₂ is present in striated muscle α-actinin and that it is necessary for α-actinin to realize its maximum gelating activity.