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Phosphatidylinositol 4,5 bisphosphate and other Phosphatidylinositide lipids binding by Actin Binding Proteins.

Profilin was the first actin-binding protein to be shown to be associated with phosphoinositide lipids (Lassing & Linberg, 1985), gelsolin too was soon added to the list (see Gelsolin and PI)(Janmey & Stossel, 1987) and this list continues to grow (table 1)(Sechi & Wehland, 2000). Five distinct protein domains whose function is to bind various phosphoinositide lipids lipids have been identified, these are PH, FYVE, PX, ENTH and FERM domains. The PIP2 binding regions of the actin binding proteins may constitute further phosphoinositide lipids binding domains. The interaction of ABPs and phosphoinositide lipids may be enhanced by the co-operation of lysophosphatidic acid (Meerschaert et al, 1998).

Protein (ABP)	PI -binding domain	Effect on Actin-Binding	References
a-actinin		Increases affinity for F-actin in muscle a-actinin.	Fukami et al, 1992; 1994; 1996
ADF/Cofilin	WAPECAPLKSKM	Binding by PIP₂ and actin are exclusive, so the lipid inhibits ADF/Cofilin actin binding function.	Fukami et al, 1994; Yonezawa et al, 1990;1991
Calponin	?	PI inhibited actin-binding	Fujii et al, 1995
CapZ	?	PIP₂ inhibits capping by CapZ.	Heiz & Cooper, 1991; DiNubile & Huang, 1997; Schafer et al, 1996.
Cortexillin	MKLLNQKEDDLKAQKLKSSKSKK	PIP₂ inhibits bundling of F-actin by cortexillins	Stock et al, 1999
ERM	KK(X)_nK/RK	PIP₂ activates ERM by revealing the cryptic actin-binding site in the N terminus.	Matsui et al, 1999; Barret et al, 2000
Filamin	FTRWCNEHLKCVSKRIANLQTDL	PI, PIP and PIP₂ inhibited cross-linking of actin filaments by filamin unlike muscle a-actinin	Furuhashi et al, 1992;
Gelsolin	KSGLKYKK	PIP₂ causes gelsolin to detach from the barbed ends of actin filaments.	Janmey & Stossel, 1987; Yu et al, 1992
gCap39		PIP₂ inhibits capping by gCap39.	Yu et al, 1990
Profilin		PIP₂ dissociates actin:profilin complexes.	Lassing & Linberg, 1985
Scinderin (Adseverin)		PIP₂ inhibits capping by scinderin.	Castillo et al, 1992
Talin			Isenberg et al,1996; Tempel et al, 1995
Tensin			Davis et al, 1991
Titin			Astier et al, 1998
Twinfilin			Palmgren et al, 2001
Vinculin		Inhibits the actin binding activity of vinculin.	Johnston & Craig, 1995; Gilmore & Burridge, 1996; Steimle et al, 1999.Huttelmaier et al, 998
Villin	YNVQRLLHVKGKKNVV		Janmey et al, 1992
WASP			Miki et al, 1996


Links

Stephen Shears Inositide web-site

PH domains

ENTH domains

PI metabolism

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