Long-range and selective autoregulation of cell-cell or cell-matrix adhesions by cadherin or integrin ligands

Shulamit Levenberg*, Ben Zion Katz, Kenneth M. Yamada, Benjamin Geiger

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

In this study we demonstrate that local stimulation of cell surface cadherins or integrins induces a enhancement of adherens junction or focal assembly, respectively, throughout the cell. N-cadherin transfected CHO cells (CHO-Ncad) were incubated with different ligands including N-cadherin extracellular domain (NEC), anti-N-cadherin antibodies, fibronectin and concanavalin A (ConA), conjugated to synthetic beads. Electron microscopic examination indicated that both cadherin- and integrin-reactive beads bound tightly to the cell surface and were apparently endocytosed after several hours of incubation. The ConA-beads remained largely at the cell surface. Immunofluorescence labeling of the cells with antibodies to different adhesion-associated molecules indicated that both NEC- and anti-N-cadherin-conjugated beads induced a major increase in the level of junction-associated cadherin and β-catenin labeling and a modest increase in junctional vinculin labeling, compared to untreated cells or cells bound to ConA-beads. FN-conjugated beads, on the other hand, significantly enhanced vinculin labeling at focal contacts and suppressed cadherin and β-catenin staining in cell-cell junctions. The cadherin-reactive beads specifically stimulated tyrosine phosphorylation at cell-cell junctions, while the FN-beads increased the levels of focal contact-associated phosphotyrosine, as shown by immunofluorescence labeling of the cells for phosphotyrosine. Inhibition of this phosphorylation by genistein resulted in a complete suppression of the effects of both types of beads. These findings indicate that specific cadherin- and integrin-mediated surface interactions can trigger positively cooperative long-range signaling events which lead to the selective assembly of cell-cell or cell-matrix adhesions, and that these signals involve tyrosine phosphorylation.

Original languageEnglish
Pages (from-to)347-357
Number of pages11
JournalJournal of Cell Science
Volume111
Issue number3
StatePublished - 1998
Externally publishedYes

Keywords

  • Adhesion-mediated signaling
  • Cadherin
  • Cell adhesion
  • Integrin
  • Tyrosine phosphorylation

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