Modulation of cell-cell adherens junctions by surface clustering of the N-cadherin cytoplasmic tail.

Cadherins mediate the formation of cell-cell adherens junctions (AJ) by homophilic interactions through their extracellular domains as well as by interacting with the actin cytoskeleton via their cytoplasmic portions. Cadherin clustering initiates cytoplasmic signaling that results in the assembly of structural components into cell-cell AJ. To elucidate the function of the cytoplasmic tail of cadherins in initiating the assembly signal, we generated and characterized a chimeric cadherin tail fused to an inert transmembrane anchor. The chimera enabled us to cluster the cadherin cytoplasmic tail in the absence of extracellular portions of the molecule. The transfected cadherin tail chimera localized to cell-cell AJ of epithelial cells, indicating that the submembrane junctional plaque has the capacity to recruit additional cadherins, with no involvement of their extracellular domains. Expression of the chimera in cells of mesenchymal origin resulted in dominant negative effects on the formation of cell-cell AJ. Surface clustering of cadherin cytoplasmic tails induced the recruitment of components and structural assembly of cell-cell AJ, thereby reversing the initial dominant-negative effects. We conclude that the cadherin cytoplasmic tail contains information required to direct the molecule to cell-cell AJ. Its function as modulator of cell-cell AJ depends on cell type and on whether the tail is clustered.