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

摘要

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 visuali zation and quantification of spatiotemporal dynamics of W-cad herin interactions across intercellular junctions in living cells using a genetically encodable FRET reporter system. Direct measurements of transjunctional cadherin interactions revealed a sudden, but par tial, loss of homophilic interactions (τ = 1.17 ± 0.06 s～(-1)) upon che lation of extracellular Ca～(2+). A cadherin mutant with reduced adhesive activity (W2A) exhibited a faster, more substantial loss of homophilic interactions (τ = 0.86 ± 0.02 s～(-1)), suggesting two types of native cadherin interactions—one that is rapidly modu lated 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 in terior where β-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.