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Rac recruits high-affinity integrin αvβ3 to lamellipodia in endothelial cell migration

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Abstract

Integrin αvβ3 has an important role in the proliferation, survival, invasion and migration of vascular endothelial cells1,2. Like other integrins, αvβ3 can exist in different functional states with respect to ligand binding. These changes involve both affinity modulation, by which conformational changes in the integrin heterodimer govern affinity for individual extracellular matrix proteins, and avidity modulation, by which changes in lateral mobility and integrin clustering affect the binding of cells to multivalent matrices. Here we have used an engineered monoclonal antibody Fab (antigen-binding fragment) named WOW-1, which binds to activated integrins αvβ3 and αvβ5 from several species3, to investigate the role of αvβ3 activation in endothelial cell behaviour. Because WOW-1 is monovalent, it is insensitive to changes in integrin clustering and therefore reports only changes in affinity. WOW-1 contains an RGD tract in its variable region and binds only to unoccupied, high-affinity integrins. By using WOW-1, we have identified the selective recruitment of high-affinity integrins as a mechanism by which lamellipodia promote formation of new adhesions at the leading edge in cell migration.

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Figure 1: Localization of high-affinity αvβ3 to cell edges.
Figure 2: Effects of manganese and matrix composition on localization of high-affinity αvβ3.
Figure 3: PI(3)K and Rac in localization of high-affinity αvβ3 to cell edges.
Figure 4: Effect of WOW-1 on cell migration.

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References

  1. Byzova, T. V., Rabbani, R., D'Souza, S. & Plow, E. F. Thromb. Haemost. 80, 726–734 (1998).

    Article  CAS  Google Scholar 

  2. Eliceiri, B. P. & Cheresh, D. A. Mol. Med. 4, 741–750 (1998).

    Article  CAS  Google Scholar 

  3. Pampori, N. et al. J. Biol. Chem. 274, 21609–21616 (1999).

    Article  CAS  Google Scholar 

  4. Smith, J. W., Vestal, D. J., Irwin, S. V., Burke, T. A. & Cheresh, D. A. J. Biol. Chem. 265, 11008 (1990).

    CAS  PubMed  Google Scholar 

  5. Frelinger, A. L., Du, X., Plow, E. F. & Ginsberg, M. H. J. Biol. Chem. 266, 17106–17111 (1991).

    CAS  PubMed  Google Scholar 

  6. Cheresh, D. A. & Spiro, R. C. J. Biol. Chem. 262, 1434–1437 (1987).

    CAS  PubMed  Google Scholar 

  7. Tam, S. H., Sassoli, P. M., Jordan, R. E. & Nakada, M. T. Circulation 1085–1091 (1998).

  8. Leavesley, D. I., Ferguson, G. D., Wayner, E. A. & Cheresh, D. A. J. Cell Biol. 117, 1101–1107 (1992).

    Article  CAS  Google Scholar 

  9. Diaz-Gonzalez, F., Forsyth, J., Steiner, B. & Ginsberg, M. H. Mol. Biol. Cell 7, 1939–1951 (1996).

    Article  CAS  Google Scholar 

  10. Blystone, S. D., Graham, I. L., Lindberg, F. P. & Brown, E. J. J. Cell Biol. 127, 1129–1137 (1994).

    Article  CAS  Google Scholar 

  11. Shimizu, Y., Mobley, J. L., Finkelstein, L. D. & Chan, A. S. H. J. Cell Biol. 131, 1867–1880 (1995).

    Article  CAS  Google Scholar 

  12. Zhang, J., Zhang, J., Shattil, S. J., Cunningham, M. C. & Rittenhouse, S. E. J. Biol. Chem. 271, 6265–6272 (1996).

    Article  CAS  Google Scholar 

  13. Kovacsovics, T. J. et al. J. Biol. Chem. 270, 11358–11366 (1995).

    Article  CAS  Google Scholar 

  14. Davis, P. D. et al. J. Med. Chem. 35, 994–1001 (1996).

    Article  Google Scholar 

  15. Ridley, A. J., Paterson, H. F., Johnston, C. L., Diekmann, D. & Hall, A. Cell 70, 401–410 (1992).

    Article  CAS  Google Scholar 

  16. Nobes, C. D. & Hall, A. J. Cell Biol. 144, 1235–1244 (1999).

    Article  CAS  Google Scholar 

  17. Ridley, A. J., Allen, W. E., Peppelenbosch, M. & Jones, G. E. Biochem. Soc. Symp. 65, 111–123 (1999).

    CAS  PubMed  Google Scholar 

  18. Hall, A. Science 279, 509–514 (1998).

    Article  CAS  Google Scholar 

  19. Nobes, C. D. & Hall, A. Cell 81, 53–62 (1995).

    Article  CAS  Google Scholar 

  20. Nishizaka, T., Shi, Q. & Sheetz, M. P. Proc. Natl Acad. Sci. USA 97, 692–697 (2000).

    Article  CAS  Google Scholar 

  21. Du, X. et al. Cell 65, 409–416 (1991).

    Article  CAS  Google Scholar 

  22. Savage, B., Shattil, S. J. & Ruggeri, Z. M. J. Biol. Chem. 267, 11300–11306 (1992).

    CAS  PubMed  Google Scholar 

  23. Leavesley, D. I., Schwartz, M. A., Rosenfeld, M. & Cheresh, D. A. J. Cell Biol. 121, 163–170 (1993).

    Article  CAS  Google Scholar 

  24. Schwartz, M. A. & Denninghoff, K. J. Biol. Chem. 269, 11133–11137 (1994).

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank M. Ginsberg for providing polyclonal and LIBS anti-αvβ3 antibodies, and B. Cessna for secretarial assistance. This work was supported by US Public Health Service grants to M.A.S. and S.J.S., and an American Heart Association fellowship to W.B.K.

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Correspondence to Martin Alexander Schwartz.

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Kiosses, W., Shattil, S., Pampori, N. et al. Rac recruits high-affinity integrin αvβ3 to lamellipodia in endothelial cell migration. Nat Cell Biol 3, 316–320 (2001). https://doi.org/10.1038/35060120

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  • DOI: https://doi.org/10.1038/35060120

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