Long-range and selective autoregulation of cell-cell or cell-matrix adhesions by cadherin or integrin ligands.
In this study we demonstrate that local stimulation of cell surface cadherins or integrins induces a selective enhancement of adherens junction or focal contact 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 beta-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 beta-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.
Levenberg
S
S
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Katz
B Z
BZ
Yamada
K M
KM
Geiger
B
B
D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002450:Cell Communication / Q000502:physiology; D002645:Chickens; D006224:Cricetinae; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D007365:Intercellular Junctions / Q000378:metabolism; D008024:Ligands; D019000:Phosphotyrosine / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism
D015820:Cadherins; D005353:Fibronectins; D008024:Ligands; D011506:Proteins; D016596:Vinculin; D019000:Phosphotyrosine