Abstract
VINCULIN, a prominent cytoskeletal protein at cell–substrate adhesions (focal adhesions) and cell–cell adhesions (adherens junctions)1, interacts with other cytoskeletal proteins, including talin and actin2,3. An intramolecular interaction between the head and tail domains of vinculin masks the binding sites for both proteins4,5. The exposure of cryptic binding sites may be important for promoting focal adhesion assembly. Several agents that induce the formation of focal adhesions act through the GTP-binding protein Rho6–9, which elevates phosphatidylinositol-4,5-bisphosphate (PtdInsP2) levels by activating phosphatidylinositol-4-phosphate-5-OH kinase (PtdIns-5-OH kinase)10. PtdInsP2 regulates several actin-binding proteins, including profilm11, gelsolin12 and α-actinin13, and interacts with vinculin14,15. Here we report that PtdInsP2 dissociates vinculin's head–tail interaction, unmasking its talin- and actin-binding sites. Microinjection of antibodies against PtdInsP2 inhibit assembly of stress fibres and focal adhesions.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
1. Geiger, B., Tokuyasu, K. T., Dutton, A. H. & Singer, S. J. Proc. natn. Acad. Sci. U.S.A. 77,4127-4131 (1980). 2. Burridge, K. & Mangeat, P. Nature 308, 744-746 (1984). 3. Menkel, A. R. eta/. J. CellBiol. 126, 1231-1240 (1994). 4. Johnson, R. P. & Craig, S. W. Nature 373, 261-264 (1995). 5. Johnson, R. P. & Craig, S. W. J. biol. Chem. 269,12611-12619 (1994). 6. Ridley, A. J. & Hall, A. Cell 70, 389-399 (1992). 7. Barry, S. & Critchley, D. R. J. Cell Sci. 107, 2033-2045 (1994). 8. Chrzanowska-Wodnicka, M. & Burridge, K. J. Cell Sci. 107, 3543-3654 (1994). 9. Seufferlein, T. & Rozengurt, E. J. biol. Chem. 269, 9345-9351 (1994). 10. Chong, L D., Traynor-Kaplan, A., Bokoch, G. M. & Schwartz, M. A. Cell 79, 507-513 (1994). 11. Lassing, I. & Lindberg, U. Nature 314, 472-474 (1985). 12. Janmey, P. A. & Stossel, T. P. Nature 325, 362-364 (1987). 13. Fukami, K. eta/. Nature 359,150-152 (1992). 14. Fukami, K., Endo, T., Imamura, M. & Takenawa, T. J. biol. Chem. 269,1518-1522 (1994). 15. Johnson, R. P. & Craig, S. W. Biochem. biophys. Res. Com/nun. 210,159-164 (1995). 16. Wood, C. K., Turner, C. E., Jackson, P. & Critchley, D. R. J. Cell Sci. 107, 709-717 (1994). 17. McNamee, H. M., Ingber, D. E. & Schwartz, M. A. J. Cell Biol. 121, 673-678 (1992). 18. Fukami, K. eta/. Proc. natn. Acad. Sci. U.S.A. 85, 9057-9061 (1988). 19. Burridge, K., Turner, C. E. & Romer, L. H. J. Cell Biol. 119, 893-903 (1992). 20. Bockholt, S. M. & Burridge, K. J. biol. Chem. 268,14565-14567 (1993). 21. Evans, R. R., Robson, R. M. & Stromer, M. H. J. biol. Chem. 259, 3916-3924 (1984). 22. Turner, C. E. & Burridge, K. Eur. J. Cell Biol. 49, 202-206 (1989). 23. Groesch, M. E. & Otto, J. J. Cell Mot/7. Cytoskel. 15, 41-50 (1990). 24. Smith, D. B. & Johnson, K. S. Gene 67, 31-40 (1988). 25. Laemmli, U. K. Nature 227, 680-685 (1970). 26. Spudich, J. A. & Watt, S. J. biol. Chem. 246, 4866-4871 (1971). 27. Nuckolls, G. H., Romer, L. H. & Burridge, K. J. Cell Sci. 102, 753-762 (1992). 28. Horwitz, A., Duggan, K., Buck, C., Beckerle, M. C. & Burridge, K. Nature 320,531-533 (1986). 29. Miyamoto, S., Akiyama, S. K. & Yamada, K. M. Science 267, 883-885 (1995). 30. Payrastre, B. et a/. J. Cell Biol. 115,121-128 (1991).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gilmore, A., Burridge, K. Regulation of vinculin binding to talin and actin by phosphatidyl-inositol-4-5-bisphosphate. Nature 381, 531–535 (1996). https://doi.org/10.1038/381531a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/381531a0
This article is cited by
-
Allosteric activation of vinculin by talin
Nature Communications (2023)
-
Isotherm kinetics of PIP2 bound gelsolin inactivation
Journal of Thermal Analysis and Calorimetry (2023)
-
Complete Model of Vinculin Suggests the Mechanism of Activation by Helical Super-Bundle Unfurling
The Protein Journal (2022)
-
Respiratory metabolites in bronchoalveolar lavage fluid (BALF) and exhaled breath condensate (EBC) can differentiate horses affected by severe equine asthma from healthy horses
BMC Veterinary Research (2020)
-
Vinculins interaction with talin is essential for mammary epithelial differentiation
Scientific Reports (2019)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.