Mechanism of the interaction of human platelet profilin with actin

doi:10.1083/jcb.113.5.1081

This Article

	Full Text (PDF, 1085K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Goldschmidt-Clermont, P. J.
	Articles by Pollard, T. D.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Goldschmidt-Clermont, P. J.
	Articles by Pollard, T. D.


Social Bookmarking

	What's this?

ARTICLES

Mechanism of the interaction of human platelet profilin with actin

PJ Goldschmidt-Clermont, LM Machesky, SK Doberstein and TD Pollard
Department of Cell Biology and Anatomy, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

We have reexamined the interaction of purified platelet profilin with actin and present evidence that simple sequestration of actin monomers in a 1:1 complex with profilin cannot explain many of the effects of profilin on actin assembly. Three different methods to assess binding of profilin to actin show that the complex with platelet actin has a dissociation constant in the range of 1 to 5 microM. The value for muscle actin is similar. When bound to actin, profilin increases the rate constant for dissociation of ATP from actin by 1,000-fold and also increases the rate of dissociation of Ca2+ bound to actin. Kinetic simulation showed that the profilin exchanges between actin monomers on a subsecond time scale that allows it to catalyze nucleotide exchange. On the other hand, polymerization assays give disparate results that are inconsistent with the binding assays and each other: profilin has different effects on elongation at the two ends of actin filaments; profilin inhibits the elongation of platelet actin much more strongly than muscle actin; and simple formation of 1:1 complexes of actin with profilin cannot account for the strong inhibition of spontaneous polymerization. We suggest that the in vitro effects on actin polymerization may be explained by a complex mechanism that includes weak capping of filament ends and catalytic poisoning of nucleation. Although platelets contain only 1 profilin for every 5-10 actin molecules, these complex reactions may allow substoichiometric profilin to have an important influence on actin assembly. We also confirm the observation of I. Lassing and U. Lindberg (1985. Nature [Lond.] 318:472- 474) that polyphosphoinositides inhibit the effects of profilin on actin polymerization, so lipid metabolism must also be taken into account when considering the functions of profilin in a cell.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Baek, K., Liu, X., Ferron, F., Shu, S., Korn, E. D., Dominguez, R. (2008). Modulation of actin structure and function by phosphorylation of Tyr-53 and profilin binding. Proc. Natl. Acad. Sci. USA 105: 11748-11753 [Abstract] [Full Text]
Syriani, E., Gomez-Cabrero, A., Bosch, M., Moya, A., Abad, E., Gual, A., Gasull, X., Morales, M. (2008). Profilin induces lamellipodia by growth factor-independent mechanism. FASEB J. 22: 1581-1596 [Abstract] [Full Text]
Wen, K.-K., McKane, M., Houtman, J. C. D., Rubenstein, P. A. (2008). Control of the Ability of Profilin to Bind and Facilitate Nucleotide Exchange from G-actin. J. Biol. Chem. 283: 9444-9453 [Abstract] [Full Text]
Gungabissoon, R. A., Bamburg, J. R. (2003). Regulation of Growth Cone Actin Dynamics by ADF/Cofilin. J. Histochem. Cytochem. 51: 411-420 [Abstract] [Full Text]
Dos Remedios, C. G., Chhabra, D., Kekic, M., Dedova, I. V., Tsubakihara, M., Berry, D. A., Nosworthy, N. J. (2003). Actin Binding Proteins: Regulation of Cytoskeletal Microfilaments. Physiol. Rev. 83: 433-473 [Abstract] [Full Text]
Nyman, T., Page, R., Schutt, C. E., Karlsson, R., Lindberg, U. (2002). A Cross-linked Profilin-Actin Heterodimer Interferes with Elongation at the Fast-growing End of F-actin. J. Biol. Chem. 277: 15828-15833 [Abstract] [Full Text]
Palmgren, S., Vartiainen, M., Lappalainen, P. (2002). Twinfilin, a molecular mailman for actin monomers. J. Cell Sci. 115: 881-886 [Abstract] [Full Text]
Yarmola, E. G., Parikh, S., Bubb, M. R. (2001). Formation and Implications of a Ternary Complex of Profilin, Thymosin beta 4, and Actin. J. Biol. Chem. 276: 45555-45563 [Abstract] [Full Text]
Lu, J., Pollard, T. D. (2001). Profilin Binding to Poly-L-Proline and Actin Monomers along with Ability to Catalyze Actin Nucleotide Exchange Is Required for Viability of Fission Yeast. Mol. Biol. Cell 12: 1161-1175 [Abstract] [Full Text]
Guillen, G., Lopez-Sanchez, L. M.L., Roman-Roque, C. S., Sanchez, F., Villanueva, M. A. (2001). Biochemical Characterization of Profilin from Seeds of Phaseolus vulgaris L.. Plant Cell Physiol 42: 54-62 [Abstract] [Full Text]
TAMURA, M., YANAGIHARA, N., TANAKA, H., OSAJIMA, A., HIRANO, T., HIGASHI, K., YAMADA, K. M., NAKASHIMA, Y., HIRANO, H. (2000). Activation of DNA Synthesis and AP-1 by Profilin, an Actin-Binding Protein, via Binding to a Cell Surface Receptor in Cultured Rat Mesangial Cells. J. Am. Soc. Nephrol. 11: 1620-1630 [Abstract] [Full Text]
Wolven, A. K., Belmont, L. D., Mahoney, N. M., Almo, S. C., Drubin, D. G. (2000). In Vivo Importance of Actin Nucleotide Exchange Catalyzed by Profilin. JCB 150: 895-904 [Abstract] [Full Text]
TAMURA, M., TANAKA, H., YASHIRO, A., OSAJIMA, A., OKAZAKI, M., KUDO, H., DOI, Y., FUJIMOTO, S., HIGASHI, K., NAKASHIMA, Y., HIRANO, H. (2000). Expression of Profilin, an Actin-Binding Protein, in Rat Experimental Glomerulonephritis and Its Upregulation by Basic Fibroblast Growth Factor in Cultured Rat Mesangial Cells. J. Am. Soc. Nephrol. 11: 423-433 [Abstract] [Full Text]
Geese, M, Schluter, K, Rothkegel, M, Jockusch, B., Wehland, J, Sechi, A. (2000). Accumulation of profilin II at the surface of Listeria is concomitant with the onset of motility and correlates with bacterial speed. J. Cell Sci. 113: 1415-1426 [Abstract]
Kang, F., Purich, D. L., Southwick, F. S. (1999). Profilin Promotes Barbed-end Actin Filament Assembly without Lowering the Critical Concentration. J. Biol. Chem. 274: 36963-36972 [Abstract] [Full Text]
Schluter, K, Schleicher, M, Jockusch, B. (1998). Effects of single amino acid substitutions in the actin-binding site on the biological activity of bovine profilin I. J. Cell Sci. 111: 3261-3273 [Abstract]
Grabski, S., Arnoys, E., Busch, B., Schindler, M. (1998). Regulation of Actin Tension in Plant Cells by Kinases and Phosphatases. Plant Physiol. 116: 279-290 [Abstract] [Full Text]
Van Aelst, L., D'Souza-Schorey, C. (1997). Rho GTPases and signaling networks. Genes Dev. 11: 2295-2322 [Full Text]
Roy, C., Martin, M., Mangeat, P. (1997). A Dual Involvement of the Amino-terminal Domain of Ezrin in F- and G-actin Binding. J. Biol. Chem. 272: 20088-20095 [Abstract] [Full Text]
Ayscough, K. R., Stryker, J., Pokala, N., Sanders, M., Crews, P., Drubin, D. G. (1997). High Rates of Actin Filament Turnover in Budding Yeast and Roles for Actin in Establishment and Maintenance of Cell Polarity Revealed Using the Actin Inhibitor Latrunculin-A. JCB 137: 399-416 [Abstract] [Full Text]
Crawford, L. E., Milliken, E. E., Irani, K., Zweier, J. L., Becker, L. C., Johnson, T. M., Eissa, N. T., Crystal, R. G., Finkel, T., Goldschmidt-Clermont, P. J. (1996). Superoxide-mediated Actin Response in Post-hypoxic Endothelial Cells. J. Biol. Chem. 271: 26863-26867 [Abstract] [Full Text]
Perelroizen, I., Didry, D., Christensen, H., Chua, N.-H., Carlier, M.-F. (1996). Role of Nucleotide Exchange and Hydrolysis in the Function of Profilin in Actin Assembly. J. Biol. Chem. 271: 12302-12309 [Abstract] [Full Text]
Heldman, A. W., Kandzari, D. E., Tucker, R. W., Crawford, L. E., Fearon, E. R., Koblan, K. S., Goldschmidt-Clermont, P. J. (1996). EJ-Ras Inhibits Phospholipase C{gamma}1 but Not Actin Polymerization Induced by Platelet-Derived Growth Factor-BB via Phosphatidylinositol 3-Kinase. Circ. Res. 78: 312-321 [Abstract] [Full Text]
Rothkegel, M, Mayboroda, O, Rohde, M, Wucherpfennig, C, Valenta, R, Jockusch, B. (1996). Plant and animal profilins are functionally equivalent and stabilize microfilaments in living animal cells. J. Cell Sci. 109: 83-90 [Abstract]
Ostrander, D. B., Gorman, J. A., Carman, G. M. (1995). Regulation of Profilin Localization in Saccharomyces cerevisiae by Phosphoinositide Metabolism. J. Biol. Chem. 270: 27045-27050 [Abstract] [Full Text]
Sohn, R. H., Chen, J., Koblan, K. S., Bray, P. F., Goldschmidt-Clermont, P. J. (1995). Localization of a Binding Site for Phosphatidylinositol 4,5-Bisphosphate on Human Profilin. J. Biol. Chem. 270: 21114-21120 [Abstract] [Full Text]
Addo, J. B., Bray, P. F., Grigoryev, D., Faraday, N., Goldschmidt-Clermont, P. J. (1995). Surface Recruitment but Not Activation of Integrin {alpha}IIb�3 (GPIIb-IIIa) Requires a Functional Actin Cytoskeleton. Arterioscler. Thromb. Vasc. Bio. 15: 1466-1473 [Abstract] [Full Text]
Perelroizen, I., Carlier, M.-F., Pantaloni, D. (1995). Binding of Divalent Cation and Nucleotide to G-actin in the Presence of Profilin. J. Biol. Chem. 270: 1501-1508 [Abstract] [Full Text]
Wheatley, S, Kulkarni, S, Karess, R (1995). Drosophila nonmuscle myosin II is required for rapid cytoplasmic transport during oogenesis and for axial nuclear migration in early embryos. Development 121: 1937-1946 [Abstract]
Stossel, T. (1993). On the crawling of animal cells. Science 260: 1086-1094 [Abstract]
Mimuro, H., Suzuki, T., Suetsugu, S., Miki, H., Takenawa, T., Sasakawa, C. (2000). Profilin Is Required for Sustaining Efficient Intra- and Intercellular Spreading of Shigella flexneri. J. Biol. Chem. 275: 28893-28901 [Abstract] [Full Text]
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. JCB 155: 251-260 [Abstract] [Full Text]