Restructuring of focal adhesion plaques by PI 3-kinase: Regulation by PtdIns (3,4,5)-P3 binding to α-actinin

J. A. Greenwood, A. B. Theibert, G. D. Prestwich, J. E. Murphy-Ullrich

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

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 α-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 α-actinin in PDGF-treated cells. Further evidence demonstrated that activation of PI 3-kinase by PDGF induced a decrease in the association of α-actinin with the integrin β 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.

Original languageEnglish (US)
Pages (from-to)627-641
Number of pages15
JournalJournal of Cell Biology
Volume150
Issue number3
DOIs
StatePublished - Aug 7 2000
Externally publishedYes

Keywords

  • Cell motility
  • Integrin
  • PDGF
  • Phosphoinositide 3-kinase
  • Vinculin

ASJC Scopus subject areas

  • Cell Biology

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