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Journal Article

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


Schuman,  E. M.
Synaptic Plasticity Department, Max Planck Institute for Brain Research, Max Planck Society;

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Kim, S. A., Tai, C.-Y., Mok, L.-P., Mosser, E. A., & Schuman, E. M. (2011). Calcium-dependent dynamics of cadherin interactions at cell-cell junctions. Proc. Natl. Acad. Sci. U. S. A., 108(24), 9857-9862.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002E-1CEF-C
Cadherins play a key role in the dynamics of cell-cell contact formation and remodeling of junctions and tissues. Cadherin-cadherin interactions are gated by extracellular Ca(2+), which serves to rigidify the cadherin extracellular domains and promote trans junctional interactions. Here we describe the direct visualization and quantification of spatiotemporal dynamics of N-cadherin interactions across intercellular junctions in living cells using a genetically encodable FRET reporter system. Direct measurements of transjunctional cadherin interactions revealed a sudden, but partial, loss of homophilic interactions (tau = 1.17 +/- 0.06 s(-1)) upon chelation of extracellular Ca(2+). A cadherin mutant with reduced adhesive activity (W2A) exhibited a faster, more substantial loss of homophilic interactions (tau = 0.86 +/- 0.02 s(-1)), suggesting two types of native cadherin interactions-one that is rapidly modulated by changes in extracellular Ca(2+) and another with relatively stable adhesive activity that is Ca(2+) independent. The Ca(2+)-sensitive dynamics of cadherin interactions were transmitted to the cell interior where beta-catenin translocated to N-cadherin at the junction in both cells. These data indicate that cadherins can rapidly convey dynamic information about the extracellular environment to both cells that comprise a junction.