The actin cytoskeleton helps stabilize the cadherin clusters that connect adjacent cells, Hong et al. reveal.
Despite cadherin’s reputation as an adhesion molecule, an individual cadherin molecule isn’t very sticky. Instead, cadherins team up to create adherens junctions that fasten cells together. The process begins when an individual cadherin on the surface of one cell grabs a cadherin on a neighboring cell. This interaction enables each of the cadherin molecules to cling to other cadherins on the same cell, forming adhesive clusters that hold the cells together. Although researchers knew that adherens junctions connect to the actin cytoskeleton, they haven’t been able to demonstrate actin’s role in cadherin-based adhesion.
Hong et al. found that tailless cadherin molecules that couldn’t link to actin formed ephemeral clumps that sped around within cell–cell contacts. The team then put the tailless cadherins on a leash, adding to them a fragment of α-catenin that ties them to actin filaments. These attached cadherins gathered in long-lasting groups that moved toward the apical surface of the cell. The cadherin clusters dispersed when the researchers treated the cells with the actin-depolymerizing drug latrunculin A, confirming that the actin cytoskeleton helps maintain the clusters. Actin and cadherin turnover were also required for the clusters’ movement to the apical surface.
Overall, the study shows that actin promotes clustering by limiting cadherin diffusion within intercellular junctions. Thus, cells might be able to adjust the strength and dynamics of adherens junctions by changing the number and strength of the bonds between the actin cytoskeleton and cadherin clusters.
Text by Mitch Leslie