EDInfo Biomedical Sciences Maciver Lab. Home ABP  A-Z Encyclopaedia Amoebae Protist Links Cytoskeleton Links Site Index

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


Stephen Shears Inositide web-site PH domains ENTH domains  PI metabolism


Astier, C., Raynaud, F., Lebart, M.-C., Roustan, C. & Benyamin, Y. (1998) Binding of a native titin fragment to actin is regulated by PIP2., FEBS Letters. 429, 95-98.

Barret, C., Roy, C., Montcourrier, P., Mangeat, P. & Niggli, V. (2000) Mutagenesis of the phosphatidylinositol 4,5-bisphsophate (PIP2) binding site in the NH2-terminal domain of ezrin correlates with its altered cellular distribution., J.Cell Biol. 151, 1067-1079.

Castillo, A. R. D., Vitale, M. L. & Trifaro, J.-M. (1992) Ca2+ and pH Determine the Interaction of Chromaffin Cell Scinderin with Phosphatidylserine and Phosphatidylinositol 4,5,-Biphosphate and Its Cellular Distribution During Nicotinic-receptor Stimulation and Protein Kinase C Activation, J.Cell Biol. 119, 797-810.

Chellaiah, M. & Hruska, K. (1996) Osteopontin stimulates gelsolin-associated phosphoinositide levels and phosphatidylinositol trisphosphate-hydroxyl kinase, Mol.Biol.Cell. 7, 743-753.

Davis , S., Lu, M. L., Lo, S. H., Lin , S., Butler, J. A., Druker , B. J., Roberts , T. M., An, Q. & Chen, L. B. (1991) Presence of an SH2 domain in the actin-binding protein tensin., Science. 252, 712-715.

DiNubile, M. J. & Huang, S. (1997) High concentrations of phosphatidylinositol-4,5-bisphosphate may promote actin filament growth by three potential mechanisms: Inhibiting capping by neutrophil lysates, severing actin filaments and removing capping protein-b2 from barbed ends., Biochim.Biophys.Acta. 1358, 261-278.

Fujii, T., Yamana, K., Ogoma, Y. & Kondo, Y. (1995) Interaction of calponin with phospholipids., J.Biochem. 117, 999-1003.

Fukami, K., Furuhashi, K., Inagaki, M., Endo, T., Hatano, S. & Takenawa, T. (1992) Requirement of phosphatidylinositol 4,5-bisphosphate for a-actinin function., Nature. 359, 150-152.

Fukami, K., Endo, T., Imamura, M. & Takenawa, T. (1994) a-Actinin and vinculin are PIP2-binding proteins involved in signaling by tyrosine kinase, J. Biol. Chem. 269, 1518-1522.

Fukami, K., Sawada, N., Endo, T. & Takenawa, T. (1996) Identification of a phosphatidylinositol 4,5-bisphosphate-binding site in chicken skeletal-muscle alpha-actinin, J. Biol.Chem. 271, 2646-2650.

Furuhashi, K., Inagaki, M., Hatano, S., Fukami, K. & Takenawa, T. (1992) Inositol phospholipid-induced suppression of F-actin-gelating activity of smooth muscle filamin., Biochem.Biophys.Res.Commun. 184, 1261-1265.

Gilmore, A. & Burridge, K. (1996) Regulation of vinculin binding to talin and actin by phosphatidyl-inositol-4-5-bisphosphate, Nature. 381, 531-535.

Goldschmidt-Clermont, P. J., Machesky, L. M., Baldassare, J. J. & Pollard, T. D. (1990) The actin-binding protein profilin binds to PIP2 and inhibits its hydrolysis by phospholipase-c, Science. 247, 1575-1578.

Hansson, A., Skoglund, G., Lassing, I., Lindberg, U. & Ingelman-Sundberg, M. (1988) Protein-kinase c-dependent phosphorylation of profilin is specifically stimulated by phosphatidylinositol bisphosphate (pip2), Biochem.Biophys.Res.Comm. 150, 526-531.

Heiss, S. G. & Cooper, J. A. (1991) Regulation of CapZ, an Actin Capping Protein of chicken Muscle, by Anionic Phospholipids, Biochemistry. 30, 8753--8758.

Hüttelmaier, S., Mayboroda, O., Harbeck, B., Jarchau, T., Jockusch, B. M. & Rüdiger, M. (1998) The interaction of cell-contact proteins VASP and vinculin is regulated by phosphatidylinositol-4,5-bisphosphate, Current Biol. 8, 479-488.

Isenberg, G., Niggli, V., Pieper, U., Kaufmann, S. & Goldmann, W. H. (1996) Probing phosphatidylinostiolphosphates and adenosinenucleotides on talin nucleated actin polymerization, FEBS letters. 397, 316-320.

Janmey, P. A. & Stossel, T. P. (1987) Modulation of gelsolin function by phosphatidylinositol 4,5-bisphosphate, Nature. 325, 362-364.

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.

Johnson, R. P. & Craig, S. W. (1995) The carboxy-terminal tail domain of vinculin contains a cryptic binding site for acidic phospholipids, Biochem.Biophys.Res.Comm. 210, 159-164.

Kraus-Friedman, N. (1994) Signal transduction and calcium: a suggested role for the cytoskeleton in inositol 1,4,5-trisphosphate action, Cell Mot. and Cytoskeleton. 28, 279-284.

Lambrechts, A., Verschelde, J.-L., Jonckheere, V., Goethals, M., Vandekerckhove, J. & Ampe, C. (1997) The mammalian profilin isoforms display complementary affinities for PIP2 and proline-rich sequences, EMBO J. 16, 484-494.

Lambrechts, A., Van Damme, J., Goethals, M., Vandekerckhove, J. & Ampe, C. (1995) Purification and characterization of bovine profilin II actin, poly(L-proline) and inositolphospholipid binding, Eur. J. Biochem. 230, 281-286.

Lassing, I. & Lindberg, U. (1985) Specific interaction between phosphatidylinositol 4,5-bisphosphate and profilactin, Nature. 314, 472-474.

Matsui, T., Yonemura, S., Tsukita, S. & Tsukita, S. (1999) Activation of ERM proteins in vivo by Rho involves phosphatidylinositol 4-phosphate 5-kinase and not ROCK kinases., Current Biology. 9, 1259-1262.

Meerschaert, K., DeCorte, V., DeVille, Y., Vandekerckhove, J. & Gettemans, J. (1998) Gelsolin and functionally similar actin-binding proteins are regulated by lysophosphatidic acid, EMBO J. 17, 5923-5932.

Ojala, P. J., Paavilainen, V. & Lappalainen, P. (2001) Identification of yeast cofilin residues specific for actin monomer and PIP2 binding., Biochemistry. 40, 15562-15569.

Palmgren, S., Ojala, P. J., Wear, M. A., Cooper, J. A. & Lappalainen, P. (2001) Interactions with PIP2, ADP-actin monomers, and capping protein regulate the activity and localization of yeast twinfilin., J. Cell Biol. 155, 251-260.

Martel, V., Racaud-Sultan, C., Dupe, S., Marie, C., Paulhe, F., Galmiche, A., Block, M. R. & Albiges-Rizo, C. (2001) Conformation, localization, and intergrin binding of talin depend on its interaction with phosphoinositides., J. Biol.Chem. 276, 21217-21227.

Miki, H., Miura, K. & Takenawa, T. (1996) N-WASP, a novel actin-depolymerizing protein, regulates the cortical cytoskeletal arrangement in a PIP2-dependent manner downstream of tyrosine kinases, EMBO J. 15, 5326-5335.

Rosales, C., Jones, S. L., McCourt, D. & Brown, E. J. (1994) Bromophenacyl bromide binding to the actin-bundling protein 1-plastin inhibits inositol trisphosphate-independent increase in Ca2+ in human neutrophils, Cell Biology. 91, 3534-3538.

Schafer, D. A., Jennings, P. B. & Cooper, J. A. (1996) Dynamics of capping protein and actin assembly in vitro: Uncapping barbed ends by polyphosphoinositides., J.Cell Biol. 135, 169-179.

Sechi, A.S. & Wehland, J. (2000). "The actin cytoskeleton and plasma membrane connection: PtdIns(4,5)P2 influences cytoskeletal protein activity at the plasma membrane. J.Cell Sci. 112, 3685-3695.

Shibasaki, F., Fukami, K., Fukui, Y. & Takenawa, T. (1994) Phosphatidylinositol 3-kinase binds to a-actinin through the p85 subunit., Biochem.J. 302, 551-557.

Steimle, P. A., Hoffert, J. D., Adey, N. B. & Craig, S. W. (1999) Polyphosphoinositides inhibit the interaction of vinculin with actin filaments., J.Biol.Chem. 274, 18414-18420.

Stock, A., Steinmertz, M. O., Janmey, P. A., Aebi, U., Gerisch, G., Kammerer, R. A., Weber, I. & Faix, J. (1999) Domain analysis of cortexillin I: actin bundling, PIP2-binding and the rescue of cytokinesis., EMBO. 18, 5274-5284.

Sugiyama, T., Matsuda, Y. & Mikoshiba, K. (2000) Inositol 1,4,5-trisphosphate receptor associated with focal contact cytoskeletal proteins., FEBS letters.

Takenawa, T. & Itoh, T. (2001) Phosphoinositides, key molecules for regulation of actin cytoskeletal organization and membrane traffic from the plasma membrane., BBA. 1533, 190-206.

Tempel, M., Goldmann, W. H., Isenberg, G. & Sackmann, E. (1995) Interaction of the 47-kDa talin fragment and the 32-kDa vinculin fragment with acidic phospholipids: a computer analysis, Biophys.J. 69, 228-241.

Torti, M., Bertoni, A., Sinigaglia, F., Balduini, C., Payrastre, B., Plantavid, M., Chap, H. & Mauco, G. (2000) The platelet cytoskeleton regulates the aggregation-dependent synthesis of phosphatidyl 3,4-bisphosphate induced by thrombin., FEBS letters.

Watt, S. A., Kular, G., Fleming, I. N., Downes, C. P. & Lucocq, J. M. (2002) Subcellular localization of phosphatidylinositol 4,5-bisphosphate using the plackstrin homology domain of phospholipase Cd1. Biochem. J. 363, 657-666.

Xian, W., Garver, T. M., Braunlin, W. H. & Janmey, P. A. (1992) NMR and CD conformational studies of a 20 amino-acid PIP2-binding site on gelsolin, Faseb Journal. 6, A 87-A 87.

Xian, W. J., Braunlin, W. H. & Janmey, P. A. (1993) CD and NMR-studies of the conformation of a 20-amino acid PIP2-binding domain of gelsolin in mixed-solvent, Biophysical Journal. 64, 62.

Yamamoto, M., Hilgemann, D. H., Feng, S., Bito, H., Ishihara, H., Shibasaki, Y. & Yin, H. L. (2001) Phosphatidylinositol 4,5-bisphosphate induces actin stress-fiber formation and inhibits membrane ruffling in CV1 cells., J.Cell Biol. 152, 867-876.

Yonezawa, N., Nishida, E., Iida, K., Yahara, I. & Sakai, H. (1990) Inhibition of the interactions of cofilin, destrin, and deoxyribonuclease-1 with actin by phosphoinositides, J. Biol. Chem. 265, 8382-8386.

Yonezawa, N., Homma, Y., Yahara, I., Sakai, H. & Nishida, E. (1991) A short sequence responsible for both phosphoinositide binding and actin binding activities of cofilin., J. Biol. Chem. 266, 17218-17221.

Yu, F.-Z., Sun, H.-Q., Janmey, P. A. & Yin, H. L. (1992) Identification of a polyphosphoinositide-binding sequence in an actin monomer-binding domain of gelsolin, J. Biol. Chem. 267, 14616-14621.

Yu, F.-X., Johnston, P. A., Sudhof, T. C. & Yin, H. L. (1990) gCap39, a calcium ion- and polyphosphoinoitide-regulated actin capping protein, Science. 250, 1413-1414.

  EDInfo Biomedical Sciences Cytoskeletal Links Encyclopaedia of A.B.P.s The Amoebae Protozoology links Glossary of Amoeba terms   Maciver Lab Home