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 journalArticle

97 Citations (Scopus)

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

Fingerprint

Actinin
Focal Adhesions
1-Phosphatidylinositol 4-Kinase
Adhesives
Extracellular Matrix
Talin
Interference Microscopy
Paxillin
Vinculin
Lipids
phosphatidylinositol 3,4,5-triphosphate
Stress Fibers
Octoxynol
Integrins
Actins
Cell Membrane

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Restructuring of focal adhesion plaques by PI 3-kinase : Regulation by PtdIns (3,4,5)-P3 binding to α-actinin. / Greenwood, J. A.; Theibert, A. B.; Prestwich, G. D.; Murphy-Ullrich, J. E.

In: Journal of Cell Biology, Vol. 150, No. 3, 07.08.2000, p. 627-641.

Research output: Contribution to journalArticle

Greenwood, J. A. ; Theibert, A. B. ; Prestwich, G. D. ; Murphy-Ullrich, J. E. / Restructuring of focal adhesion plaques by PI 3-kinase : Regulation by PtdIns (3,4,5)-P3 binding to α-actinin. In: Journal of Cell Biology. 2000 ; Vol. 150, No. 3. pp. 627-641.
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