Inhibition of the interactions of cofilin, destrin, and deoxyribonuclease I with actin by phosphoinositides.
Cofilin is a widely distributed actin-modulating protein that has the ability to bind along the side of F-actin and to depolymerize F-actin in a pH-dependent manner. We found that phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP), and phosphatidylinositol 4,5-bisphosphate (PIP2) inhibited both actions of cofilin in a dose-dependent manner, while inositol 1,4,5-triphosphate (IP3), 1-oleoyl-2-acetylglycerol (OAG), phosphatidylserine (PS), or phosphatidylcholine (PC) had little or no effect on them. Gel filtration analyses showed that PIP2 bound to cofilin and thereby inhibited the binding of cofilin to G-actin. Destrin is a mammalian, pH-independent actin-depolymerizing protein. The actin-depolymerizing activity of destrin was also inhibited by PI, PIP, and PIP2, but not by IP3, OAG, PS, or PC. In addition, we found further that an actin-depolymerizing activity of bovine pancreas deoxyribonuclease I, a G-actin-sequestering protein, was inhibited by PIP and PIP2, but not by PI, IP3, OAG, PS, or PC. These results together with previous findings (Lassing, I., and Lindberg, U. (1985) Nature 314, 472-474; Janmey, P. A., and Stossel, T. P. (1987) Nature 325, 362-364) suggest that the sensitivity to polyphosphoinositides may be a common feature in vitro among actin-binding proteins that can bind to G-actin and regulate the state of actin polymerization.
Yonezawa
N
N
Department of Biophysics and Biochemistry, Faculty of Science, University of Tokyo, Japan.
Nishida
E
E
Iida
K
K
Yahara
I
I
Sakai
H
H
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000037:antagonists & inhibitors*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D003598:Cytoskeletal Proteins; D003850:Deoxyribonuclease I / Q000037:antagonists & inhibitors*; D051345:Destrin; D007700:Kinetics; D008840:Microfilament Proteins; D009132:Muscles / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D010716:Phosphatidylinositols / Q000494:pharmacology*; D011485:Protein Binding; D011817:Rabbits; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D013552:Swine
D051339:Actin Depolymerizing Factors; D000199:Actins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D051345:Destrin; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D010716:Phosphatidylinositols; D011994:Recombinant Proteins; D003850:Deoxyribonuclease I