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

Nature. 1992 Sep 10;359(6391):150-2. doi: 10.1038/359150a0.


Inositol phospholipid turnover is enhanced during mitogenic stimulation of cells by growth factors 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, but it is not yet understood how this control is achieved. The protein alpha-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 alpha-actinin binds to F-actin and will crosslink actin filaments, increasing the viscosity of F-actin solutions. We report here that alpha-actinin from striated muscle is an endogenous PtdInsP2-bound protein and that the specific interaction between alpha-actinin and PtdInsP2 regulates the F-actin-gelating activity of alpha-actinin. Although the F-actin-gelating activity of alpha-actinin from smooth muscle is much reduced compared with that from striated muscle, exogenous PtdInsP2 can enhance the activity of smooth muscle alpha-actinin to the level seen in striated muscles. These results show that PtdInsP2 is present in striated muscle alpha-actinin and that it is necessary for alpha-actinin to realize its maximum gelating activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinin / physiology*
  • Actins / drug effects
  • Animals
  • Blotting, Western
  • Chickens
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation
  • In Vitro Techniques
  • Muscles / physiology
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates*
  • Phosphatidylinositols / pharmacology*
  • Viscosity / drug effects


  • Actins
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols
  • phosphatidylinositol 4-phosphate
  • Actinin