An inhibition of gap-junctional communication by cadherins.

The action of Ca(2+)-dependent cell-cell adhesion molecules (cadherins) on cell-to-cell channel-mediated intercellular communication was investigated in mouse L and rat Morris hepatoma cells. These cells fail to adhere to one another in aggregation assays and thus seem to lack cell adhesion molecules. Expression of exogenous cadherin induced strong cell-cell adhesion in both cell types, but had opposite effects of communication, causing inhibition in L cells and improvement in hepatoma cells. Both cells express the connexin43 cell-to-cell channel protein. By western blot we found no cadherin-specific changes in connexin43 protein in either cell type, but connexin43 gap junctional plaque staining, i.e. connexin43 localization to cell-cell junctions, was inhibited in L cells and facilitated in hepatoma cells. In addition we found that the inhibitory effect is largely abolished by blockers of glycosylation. Cadherin-cadherin interactions are known to trigger cell type-specific intracellular signal cascades resulting in diverse end effects, and gap junctional communication/plaque formation seems a further example of such cell type-specificity.