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. 1996 May;7(5):743–753. doi: 10.1091/mbc.7.5.743

Osteopontin stimulates gelsolin-associated phosphoinositide levels and phosphatidylinositol triphosphate-hydroxyl kinase.

M Chellaiah 1, K Hruska 1
PMCID: PMC275927  PMID: 8744948

Abstract

Based on previous studies demonstrating activation of phosphatidylinositol 3-hydroxyl kinase (PI3-kinase) and stimulation of a change in cell shape, we examined the effect of osteopontin on the association of phospholipids with gelsolin, an actin-capping/severing protein. Osteopontin stimulated a rapid increase in phosphatidylinositol bisphosphate and phosphatidylinositol triphosphate levels associated with gelsolin in Triton-soluble fractions of cell lysates. The increased levels of phosphatidylinositol triphosphate associated with gelsolin were due to stimulation of PI3-kinase activity associated with gelsolin in the Triton-soluble fractions, and they were blocked by the PI3-kinase inhibitor wortmannin. Osteopontin stimulated translocation of PI3-kinase from the Triton-insoluble to Triton-soluble gelsolin. Osteopontin also decreased Triton-soluble gelsolin/actin complexes consistent with actin uncapping, and increased F-actin levels, which were also blocked by wortmannin. The osteopontin effects were mediated through binding to the alpha(v)beta 3 integrin. Taken together, our studies indicate that osteopontin/alpha(v)beta 3-mediated changes in gelsolin-associated phosphoinositide levels and PI3-kinase activity are related to stimulation of F-actin formation in osteoclasts.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alvarez J. I., Teitelbaum S. L., Blair H. C., Greenfield E. M., Athanasou N. A., Ross F. P. Generation of avian cells resembling osteoclasts from mononuclear phagocytes. Endocrinology. 1991 May;128(5):2324–2335. doi: 10.1210/endo-128-5-2324. [DOI] [PubMed] [Google Scholar]
  2. Boulikas T., Kong C. F. Multitude of inverted repeats characterizes a class of anchorage sites of chromatin loops to the nuclear matrix. J Cell Biochem. 1993 Sep;53(1):1–12. doi: 10.1002/jcb.240530802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chaponnier C., Yin H. L., Stossel T. P. Reversibility of gelsolin/actin interaction in macrophages. Evidence of Ca2+-dependent and Ca2+-independent pathways. J Exp Med. 1987 Jan 1;165(1):97–106. doi: 10.1084/jem.165.1.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chong L. D., Traynor-Kaplan A., Bokoch G. M., Schwartz M. A. The small GTP-binding protein Rho regulates a phosphatidylinositol 4-phosphate 5-kinase in mammalian cells. Cell. 1994 Nov 4;79(3):507–513. doi: 10.1016/0092-8674(94)90259-3. [DOI] [PubMed] [Google Scholar]
  5. Downes C. P., Carter A. N. Phosphoinositide 3-kinase: a new effector in signal transduction? Cell Signal. 1991;3(6):501–513. doi: 10.1016/0898-6568(91)90027-r. [DOI] [PubMed] [Google Scholar]
  6. Forscher P. Calcium and polyphosphoinositide control of cytoskeletal dynamics. Trends Neurosci. 1989 Nov;12(11):468–474. doi: 10.1016/0166-2236(89)90098-2. [DOI] [PubMed] [Google Scholar]
  7. Grondin P., Plantavid M., Sultan C., Breton M., Mauco G., Chap H. Interaction of pp60c-src, phospholipase C, inositol-lipid, and diacyglycerol kinases with the cytoskeletons of thrombin-stimulated platelets. J Biol Chem. 1991 Aug 25;266(24):15705–15709. [PubMed] [Google Scholar]
  8. Gutkind J. S., Lacal P. M., Robbins K. C. Thrombin-dependent association of phosphatidylinositol-3 kinase with p60c-src and p59fyn in human platelets. Mol Cell Biol. 1990 Jul;10(7):3806–3809. doi: 10.1128/mcb.10.7.3806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Heiss S. G., Cooper J. A. Regulation of CapZ, an actin capping protein of chicken muscle, by anionic phospholipids. Biochemistry. 1991 Sep 10;30(36):8753–8758. doi: 10.1021/bi00100a006. [DOI] [PubMed] [Google Scholar]
  10. Hofmann A., Eichinger L., André E., Rieger D., Schleicher M. Cap100, a novel phosphatidylinositol 4,5-bisphosphate-regulated protein that caps actin filaments but does not nucleate actin assembly. Cell Motil Cytoskeleton. 1992;23(2):133–144. doi: 10.1002/cm.970230206. [DOI] [PubMed] [Google Scholar]
  11. Holtrop M. E., King G. J. The ultrastructure of the osteoclast and its functional implications. Clin Orthop Relat Res. 1977 Mar-Apr;(123):177–196. [PubMed] [Google Scholar]
  12. Horton M. A., Taylor M. L., Arnett T. R., Helfrich M. H. Arg-Gly-Asp (RGD) peptides and the anti-vitronectin receptor antibody 23C6 inhibit dentine resorption and cell spreading by osteoclasts. Exp Cell Res. 1991 Aug;195(2):368–375. doi: 10.1016/0014-4827(91)90386-9. [DOI] [PubMed] [Google Scholar]
  13. Howard T., Chaponnier C., Yin H., Stossel T. Gelsolin-actin interaction and actin polymerization in human neutrophils. J Cell Biol. 1990 Jun;110(6):1983–1991. doi: 10.1083/jcb.110.6.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hruska K. A., Rolnick F., Huskey M., Alvarez U., Cheresh D. Engagement of the osteoclast integrin alpha v beta 3 by osteopontin stimulates phosphatidylinositol 3-hydroxyl kinase activity. Endocrinology. 1995 Jul;136(7):2984–2992. doi: 10.1210/endo.136.7.7540546. [DOI] [PubMed] [Google Scholar]
  15. Ikeda T., Nomura S., Yamaguchi A., Suda T., Yoshiki S. In situ hybridization of bone matrix proteins in undecalcified adult rat bone sections. J Histochem Cytochem. 1992 Aug;40(8):1079–1088. doi: 10.1177/40.8.1619274. [DOI] [PubMed] [Google Scholar]
  16. Isenberg G. Actin binding proteins--lipid interactions. J Muscle Res Cell Motil. 1991 Apr;12(2):136–144. doi: 10.1007/BF01774032. [DOI] [PubMed] [Google Scholar]
  17. Jackson T. R., Stephens L. R., Hawkins P. T. Receptor specificity of growth factor-stimulated synthesis of 3-phosphorylated inositol lipids in Swiss 3T3 cells. J Biol Chem. 1992 Aug 15;267(23):16627–16636. [PubMed] [Google Scholar]
  18. Janmey P. A., Stossel T. P. Modulation of gelsolin function by phosphatidylinositol 4,5-bisphosphate. Nature. 1987 Jan 22;325(6102):362–364. doi: 10.1038/325362a0. [DOI] [PubMed] [Google Scholar]
  19. Kouns W. C., Fox C. F., Lamoreaux W. J., Coons L. B., Jennings L. K. The effect of glycoprotein IIb-IIIa receptor occupancy on the cytoskeleton of resting and activated platelets. J Biol Chem. 1991 Jul 25;266(21):13891–13900. [PubMed] [Google Scholar]
  20. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  21. Lassing I., Lindberg U. Specific interaction between phosphatidylinositol 4,5-bisphosphate and profilactin. Nature. 1985 Apr 4;314(6010):472–474. doi: 10.1038/314472a0. [DOI] [PubMed] [Google Scholar]
  22. Lassing I., Lindberg U. Specificity of the interaction between phosphatidylinositol 4,5-bisphosphate and the profilin:actin complex. J Cell Biochem. 1988 Jul;37(3):255–267. doi: 10.1002/jcb.240370302. [DOI] [PubMed] [Google Scholar]
  23. Marchisio P. C., Cirillo D., Naldini L., Primavera M. V., Teti A., Zambonin-Zallone A. Cell-substratum interaction of cultured avian osteoclasts is mediated by specific adhesion structures. J Cell Biol. 1984 Nov;99(5):1696–1705. doi: 10.1083/jcb.99.5.1696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Marchisio P. C., Cirillo D., Teti A., Zambonin-Zallone A., Tarone G. Rous sarcoma virus-transformed fibroblasts and cells of monocytic origin display a peculiar dot-like organization of cytoskeletal proteins involved in microfilament-membrane interactions. Exp Cell Res. 1987 Mar;169(1):202–214. doi: 10.1016/0014-4827(87)90238-2. [DOI] [PubMed] [Google Scholar]
  25. Medhora M. M., Teitelbaum S., Chappel J., Alvarez J., Mimura H., Ross F. P., Hruska K. 1 alpha,25-dihydroxyvitamin D3 up-regulates expression of the osteoclast integrin alpha v beta 3. J Biol Chem. 1993 Jan 15;268(2):1456–1461. [PubMed] [Google Scholar]
  26. Moore M. A., Gotoh Y., Rafidi K., Gerstenfeld L. C. Characterization of a cDNA for chicken osteopontin: expression during bone development, osteoblast differentiation, and tissue distribution. Biochemistry. 1991 Mar 5;30(9):2501–2508. doi: 10.1021/bi00223a029. [DOI] [PubMed] [Google Scholar]
  27. Oldberg A., Franzén A., Heinegård D. Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8819–8823. doi: 10.1073/pnas.83.23.8819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Painter R. G., Ginsberg M. Concanavalin A induces interactions between surface glycoproteins and the platelet cytoskeleton. J Cell Biol. 1982 Feb;92(2):565–573. doi: 10.1083/jcb.92.2.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Payrastre B., van Bergen en Henegouwen P. M., Breton M., den Hartigh J. C., Plantavid M., Verkleij A. J., Boonstra J. Phosphoinositide kinase, diacylglycerol kinase, and phospholipase C activities associated to the cytoskeleton: effect of epidermal growth factor. J Cell Biol. 1991 Oct;115(1):121–128. doi: 10.1083/jcb.115.1.121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pollard T. D., Cooper J. A. Actin and actin-binding proteins. A critical evaluation of mechanisms and functions. Annu Rev Biochem. 1986;55:987–1035. doi: 10.1146/annurev.bi.55.070186.005011. [DOI] [PubMed] [Google Scholar]
  31. Reinholt F. P., Hultenby K., Oldberg A., Heinegård D. Osteopontin--a possible anchor of osteoclasts to bone. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4473–4475. doi: 10.1073/pnas.87.12.4473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shibasaki F., Fukami K., Fukui Y., Takenawa T. Phosphatidylinositol 3-kinase binds to alpha-actinin through the p85 subunit. Biochem J. 1994 Sep 1;302(Pt 2):551–557. doi: 10.1042/bj3020551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Stossel T. P. From signal to pseudopod. How cells control cytoplasmic actin assembly. J Biol Chem. 1989 Nov 5;264(31):18261–18264. [PubMed] [Google Scholar]
  34. Stossel T. P. On the crawling of animal cells. Science. 1993 May 21;260(5111):1086–1094. doi: 10.1126/science.8493552. [DOI] [PubMed] [Google Scholar]
  35. Weber G. F., Ashkar S., Glimcher M. J., Cantor H. Receptor-ligand interaction between CD44 and osteopontin (Eta-1). Science. 1996 Jan 26;271(5248):509–512. doi: 10.1126/science.271.5248.509. [DOI] [PubMed] [Google Scholar]
  36. Whitman M., Kaplan D. R., Schaffhausen B., Cantley L., Roberts T. M. Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation. Nature. 1985 May 16;315(6016):239–242. doi: 10.1038/315239a0. [DOI] [PubMed] [Google Scholar]
  37. Yano H., Nakanishi S., Kimura K., Hanai N., Saitoh Y., Fukui Y., Nonomura Y., Matsuda Y. Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL-2H3 cells. J Biol Chem. 1993 Dec 5;268(34):25846–25856. [PubMed] [Google Scholar]
  38. Yin H. L. Gelsolin: calcium- and polyphosphoinositide-regulated actin-modulating protein. Bioessays. 1987 Oct;7(4):176–179. doi: 10.1002/bies.950070409. [DOI] [PubMed] [Google Scholar]
  39. Zambonin-Zallone A., Teti A., Carano A., Marchisio P. C. The distribution of podosomes in osteoclasts cultured on bone laminae: effect of retinol. J Bone Miner Res. 1988 Oct;3(5):517–523. doi: 10.1002/jbmr.5650030507. [DOI] [PubMed] [Google Scholar]
  40. Zhang J., Fry M. J., Waterfield M. D., Jaken S., Liao L., Fox J. E., Rittenhouse S. E. Activated phosphoinositide 3-kinase associates with membrane skeleton in thrombin-exposed platelets. J Biol Chem. 1992 Mar 5;267(7):4686–4692. [PubMed] [Google Scholar]

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