Calcium-dependent dynamics of cadherin interactions at cell-cell junctions

Rapid calcium-sensing property of transmembrane cadherin proteins reveals coordinated adhesion and signaling across cell-cell junctions

Classic cadherins are transmembrane proteins that mediate adhesive cell-cell contacts through calcium-dependent interactions between their extracellular domains. On the intracellular side, the cadherins are functionally linked to the cytoskeleton via catenin proteins. While the structure and cellular function of the cadherins is well-studied, only little has been known so far about their interactions in living cells. Scientists in the Caltech group of Erin Schuman, now director at the MPI for Brain Research in Frankfurt, have succeeded to visualize and quantify the spatiotemporal dynamics of N-cadherin interactions across intercellular junctions in live cells using a genetically encoded fluorescence reporter system developed in the Schuman lab.

Those studies, published in the latest issue of the Proceeding of the National Academy of Science, USA, show that cadherins rapidly sense changes in the extracellular Ca2+ level: within seconds of Ca2+ depletion the cadherin molecules move apart from one another, which ultimately influences the adhesion between cells. Interestingly, this information is also transmitted across the plasma membrane to the cell interior where the cadherin´s binding partner β-catenin was found to translocate to N-cadherin at the junction in both adjacent cells. The rapid Ca2+-sensing property of cadherin molecules documented in this paper suggests a coordinated adhesion and signaling across cell-cell junctions, allowing both cells comprising the junction to access the same information at the same time.