Kovacs and Yap began their study by observing cells moving over a substrate covered with E-cadherin. They noticed that clumps of E-cadherin colocalized with both filamentous actin and components of the actin-nucleating Arp2/3 complex. Similar colocalization was apparent upon addition of E-cadherin beads. Finally, E-cadherin coimmunoprecipitated with Arp2/3 components, even in the presence of the actin-depolymerizing drug cytochalasin D.
The association suggests that cadherin ligation might trigger actin assembly by Arp2/3. “What we'd like to correct,” says Yap, “is the notion that cadherin complexes are solely binding to preformed actin filaments.” In his view, the adhesion machinery is no longer seen as an inert scaffold, but as a dynamic complex that drives changes in cell shape and movement.
The connection between E-cadherin and Arp2/3 may or may not be direct. When Yap and his colleagues know more about this interaction, they hope to disrupt it without interfering with cadherin adhesive function, thus testing the importance of the link. They will be looking for defects in processes such as compaction, when cell surfaces extend over one another. ▪