Gelsolin and Phospholipids

Gelsolin and Phospholipids
In 1984, Lassing and Linberg, raised a few eyebrows by their discovery that the well documented protein profilin, bound specifically to phosphatidylinositol 4, 5-bisphosphate, (PIP₂) a highly charged phospholipid found at the cytoplasmic leaflet of the plasma-membrane (Lassing & Linberg, 1985) (Right). This report was quickly followed by others who found that not only did other ABPs bind these lipids, but that in doing so, their actin-binding properties were modulated (e.g. Gelsolin see below). The gelsolin cap at the end of the actin filament is very tight but it was shown that PIP₂ could dissociate the complex so that actin monomers can now leave the barbed end of the filament (Janmey et al, 1987a, Janmey et al, 1987b).	PIP₂
	Gelsolin is present in inactivated cells on the barbed end of the filament, preventing further polymerization. Upon stimulation, gelsolin is removed from the filament end by the production of PIP₂. Further actin polymerization can now take place at the fast growing end, driving the cell forwards possibly by the Brownian ratchet mechanism. PIP₂also leads to the dissociation of the profilin :actin, and the cofilin:actin complexes so that more actin would be available for polymerization.
PIP₂ is known to bind many actin-binding and other proteins and to modulate their activity.


References:- Janmey, P. A., Chaponnier, C., Lind, S. E., Zaner, K. S., Stossel, T. P. & Yin, H. L. (1985) Interactions of gelsolin and gelsolin-actin complexes with actin. Effects of calcium on actin nucleation, filament severing and end blocking., Biochemstry. 24, 3714-3723. Janmey, P. A. & Stossel, T. P. (1987a) Modulation of gelsolin function by phosphatidylinositol 4,5-bisphosphate, Nature. 325, 362-364. Janmey, P. A., Iida, K., Yin, H. L. & Stossel, T. P. (1987b) Polyphosphoinositide micelles and polyphosphoinoositide-containing vesicles dissociate endogenous gelsolin-actin complexes and promote actin assembly from the fast-growing end of actin filaments blocked by gelsolin, J. Biol. Chem. 262, 12228-12236. Janmey, P. A., Lamb, J., Allen, P. G. & Matsudaira, P. T. (1992) Phosphoinositide-binding peptides derived from the sequences of gelsolin and villin, J. Biol. Chem. 267, 11818-11823. Lassing, I. & Lindberg, U. (1985) Specific interaction between phosphatidylinositol 4,5-bisphosphate and profilactin, Nature. 314, 472-474.