Original Article

Restructuring of Focal Adhesion Plaques by PI 3-Kinase: Regulation by PtdIns (3,4,5)-P₃ Binding to -Actinin

Correspondence to: Jeffrey A. Greenwood, Department of Biochemistry and Biophysics, 2103B Agricultural and Life Sciences, Oregon State University, Corvallis, OR 97331-7305. Tel:(541) 737-4997 Fax:(541) 737-0481 E-mail:jeffrey.greenwood{at}orst.edu.

Focal adhesions are an elaborate network of interconnecting proteins linking actin stress fibers to the extracellular matrix substrate. Modulation of the focal adhesion plaque provides a mechanism for the regulation of cellular adhesive strength. Using interference reflection microscopy, we found that activation of phosphoinositide 3-kinase (PI 3-kinase) by PDGF induces the dissipation of focal adhesions. Loss of this close apposition between the cell membrane and the extracellular matrix coincided with a redistribution of -actinin and vinculin from the focal adhesion complex to the Triton X-100–soluble fraction. In contrast, talin and paxillin remained localized to focal adhesions, suggesting that activation of PI 3-kinase induced a restructuring of the plaque rather than complete dispersion. Furthermore, phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5)-P₃), a lipid product of PI 3-kinase, was sufficient to induce restructuring of the focal adhesion plaque. We also found that PtdIns (3,4,5)-P₃ binds to -actinin in PDGF-treated cells. Further evidence demonstrated that activation of PI 3-kinase by PDGF induced a decrease in the association of -actinin with the integrin ß subunit, and that PtdIns (3,4,5)-P₃ could disrupt this interaction in vitro. Modification of focal adhesion structure by PI 3-kinase and its lipid product, PtdIns (3,4,5)-P₃, has important implications for the regulation of cellular adhesive strength and motility.

Key Words: cell motility, phosphoinositide 3-kinase, PDGF, integrin, vinculin

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Sprague, C. R., Fraley, T. S., Jang, H. S., Lal, S., Greenwood, J. A. (2008). Phosphoinositide Binding to the Substrate Regulates Susceptibility to Proteolysis by Calpain. J. Biol. Chem. 283: 9217-9223 [Abstract] [Full Text]  
• Friedrich, C., Endlich, N., Kriz, W., Endlich, K. (2006). Podocytes are sensitive to fluid shear stress in vitro. Am. J. Physiol. Renal Physiol. 291: F856-F865 [Abstract] [Full Text]  
• Zhang, W., Gunst, S. J. (2006). Dynamic association between {alpha}-actinin and {beta}-integrin regulates contraction of canine tracheal smooth muscle. J. Physiol. 572: 659-676 [Abstract] [Full Text]  
• Burleigh, B. A. (2005). Host Cell Signaling and Trypanosoma cruzi Invasion: Do All Roads Lead to Lysosomes?. Sci Signal 2005: pe36-pe36 [Abstract] [Full Text]  
• Bois, P. R. J., Borgon, R. A., Vonrhein, C., Izard, T. (2005). Structural Dynamics of {alpha}-Actinin-Vinculin Interactions. Mol. Cell. Biol. 25: 6112-6122 [Abstract] [Full Text]  
• Li, Q., Montalbetti, N., Shen, P. Y., Dai, X.-Q., Cheeseman, C. I., Karpinski, E., Wu, G., Cantiello, H. F., Chen, X.-Z. (2005). Alpha-actinin associates with polycystin-2 and regulates its channel activity. Hum Mol Genet 14: 1587-1603 [Abstract] [Full Text]  
• Fraley, T. S., Pereira, C. B., Tran, T. C., Singleton, C., Greenwood, J. A. (2005). Phosphoinositide Binding Regulates {alpha}-Actinin Dynamics: MECHANISM FOR MODULATING CYTOSKELETAL REMODELING. J. Biol. Chem. 280: 15479-15482 [Abstract] [Full Text]  
• Barker, T. H., Pallero, M. A., MacEwen, M. W., Tilden, S. G., Woods, A., Murphy-Ullrich, J. E., Hagood, J. S. (2004). Thrombospondin-1-induced Focal Adhesion Disassembly in Fibroblasts Requires Thy-1 Surface Expression, Lipid Raft Integrity, and Src Activation. J. Biol. Chem. 279: 23510-23516 [Abstract] [Full Text]  
• Yamaji, S., Suzuki, A., Kanamori, H., Mishima, W., Yoshimi, R., Takasaki, H., Takabayashi, M., Fujimaki, K., Fujisawa, S., Ohno, S., Ishigatsubo, Y. (2004). Affixin interacts with {alpha}-actinin and mediates integrin signaling for reorganization of F-actin induced by initial cell-substrate interaction. JCB 165: 539-551 [Abstract] [Full Text]  
• Faccio, R., Novack, D. V., Zallone, A., Ross, F. P., Teitelbaum, S. L. (2003). Dynamic changes in the osteoclast cytoskeleton in response to growth factors and cell attachment are controlled by {beta}3 integrin. JCB 162: 499-509 [Abstract] [Full Text]  
• Fraley, T. S., Tran, T. C., Corgan, A. M., Nash, C. A., Hao, J., Critchley, D. R., Greenwood, J. A. (2003). Phosphoinositide Binding Inhibits {alpha}-Actinin Bundling Activity. J. Biol. Chem. 278: 24039-24045 [Abstract] [Full Text]  
• Couchman, J. R., Vogt, S., Lim, S.-T., Lim, Y., Oh, E.-S., Prestwich, G. D., Theibert, A., Lee, W., Woods, A. (2002). Regulation of Inositol Phospholipid Binding and Signaling through Syndecan-4. J. Biol. Chem. 277: 49296-49303 [Abstract] [Full Text]  
• Kulkarni, S., Goll, D. E., Fox, J. E. B. (2002). Calpain Cleaves RhoA Generating a Dominant-negative Form That Inhibits Integrin-induced Actin Filament Assembly and Cell Spreading. J. Biol. Chem. 277: 24435-24441 [Abstract] [Full Text]  
• Orr, A. W., Pallero, M. A., Murphy-Ullrich, J. E. (2002). Thrombospondin Stimulates Focal Adhesion Disassembly through Gi- and Phosphoinositide 3-Kinase-dependent ERK Activation. J. Biol. Chem. 277: 20453-20460 [Abstract] [Full Text]  
• Lum, A. F. H., Green, C. E., Lee, G. R., Staunton, D. E., Simon, S. I. (2002). Dynamic Regulation of LFA-1 Activation and Neutrophil Arrest on Intercellular Adhesion Molecule 1 (ICAM-1) in Shear Flow. J. Biol. Chem. 277: 20660-20670 [Abstract] [Full Text]  
• Guvakova, M. A., Adams, J. C., Boettiger, D. (2002). Functional role of {alpha}-actinin, PI 3-kinase and MEK1/2 in insulin-like growth factor I receptor kinase regulated motility of human breast carcinoma cells. J. Cell Sci. 115: 4149-4165 [Abstract] [Full Text]  
• Chellaiah, M. A., Biswas, R. S., Yuen, D., Alvarez, U. M., Hruska, K. A. (2001). Phosphatidylinositol 3,4,5-Trisphosphate Directs Association of Src Homology 2-containing Signaling Proteins with Gelsolin. J. Biol. Chem. 276: 47434-47444 [Abstract] [Full Text]  
• Laukaitis, C. M., Webb, D. J., Donais, K., Horwitz, A. F. (2001). Differential Dynamics of {alpha}5 Integrin, Paxillin, and {alpha}-Actinin during Formation and Disassembly of Adhesions in Migrating Cells. JCB 153: 1427-1440 [Abstract] [Full Text]  
• Yamada, K. M., Araki, M. (2001). Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J. Cell Sci. 114: 2375-2382 [Abstract] [Full Text]  
• Izaguirre, G., Aguirre, L., Hu, Y.-P., Lee, H. Y., Schlaepfer, D. D., Aneskievich, B. J., Haimovich, B. (2001). The Cytoskeletal/Non-muscle Isoform of alpha -Actinin Is Phosphorylated on Its Actin-binding Domain by the Focal Adhesion Kinase. J. Biol. Chem. 276: 28676-28685 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents