Requirement of phosphatidylinositol 4,5-bisphosphate for alpha-actinin function.
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.
Fukami
K
K
Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Japan.
Furuhashi
K
K
Inagaki
M
M
Endo
T
T
Hatano
S
S
Takenawa
T
T
D000185:Actinin / Q000502:physiology*; D000199:Actins / Q000187:drug effects; D000818:Animals; D015153:Blotting, Western; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D009132:Muscles / Q000502:physiology; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000494:pharmacology*; D014783:Viscosity / Q000187:drug effects
D000199:Actins; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C037178:phosphatidylinositol 4-phosphate; D000185:Actinin