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

Abstract

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.

Role of RhoA activation in the growth and morphology of a murine prostate tumor cell line

“…Two downstream targets of RhoA activation promote actin stress ®ber formation: (1) activation of phosphatidylinositol 5-kinase (Chong et al, 1994) whose lipid product phosphatidylinositol 3,4,5-bisphosphate activates a-actinin, an actin binding protein required for the proper assembly of actin stress ®bers (Fukami et al, 1992); and (2) activation of Rho kinase which phosphorylates myosin light chain allowing binding to F-actin and the development of the contractile bundle (Amano et al, 1997). Actin stress ®bers connect at one end to the plasma membrane at specialized sites called focal contacts where the external surface of the plasma membrane is attached to the substratum.…”

Phosphatidylinositol 4,5‐bisphosphate specifically stimulates PP60c‐src catalyzed phosphorylation of gelsolin and related actin‐binding proteins

“…Based on the structural and functional similarties between members of the gelsolin family, we hypothesize that severin from Dictyostelium discoideum and villin are also candidates for pp60 c~src phosphorylation. A similar role for PIP 2 may also apply to other cytoskeleton regulatory proteins involved in signal transduction pathways leading to microfilament rearrangements, such as vinculin [60] and cc-actinin [61].…”

Identification of a Phosphatidylinositol 4,5-Bisphosphate-binding Site in Chicken Skeletal Muscle α-Actinin

“…The fact that ␣-actinin is found at focal contacts where actin is anchored to a variety of intercellular structures in non-muscle cells suggests that ␣-actinin plays some role in the linkage between the plasma membrane and actin. We previously reported that ␣-actinin from skeletal muscle contains large amounts of PIP 2 , whereas that from smooth muscle contains little (1). Interestingly, the addition of PIP 2 to smooth muscle ␣-actinin increases the gelation activity of actin to the level produced by skeletal muscle ␣-actinin, suggesting that PIP 2 plays important roles in the organization of the cytoskeleton.…”