Cadherin clusters solidify adhesions

Strale et al. reveal that interactions between neighboring E-cadherin (Ecad) molecules help to strengthen their connection to the actin cytoskeleton and stabilize cell–cell contacts.

Ecad is the major component of adherens junctions, holding cells together by forming “trans” interactions with Ecad molecules in the plasma membrane of adjacent cells. Crystal structures of Ecad indicate that the protein can also form “cis” interactions with Ecad molecules in the same cell membrane, but whether these interactions help organize Ecad in vivo, and how this might affect the function of adherens junctions, remains unclear.

Using gold-labeled nanobodies and electron microscopy to detect single Ecad molecules within the plasma membrane, Strale et al. found that wild-type Ecad was organized into small clusters of 2–10 molecules. These clusters were dispersed by a point mutation that abolishes Ecad’s cis-interaction site. Surprisingly, however, cis-mutant Ecad was still able to support the assembly of adherens junctions between epithelial cells, although Ecad’s stability within these junctions was decreased when it was unable to form oligomeric clusters.

Disrupting Ecad’s cis interactions also reduced the association of adherens junctions with the actin cytoskeleton, perhaps because clusters of Ecad molecules are less likely to let go of actin filaments. Adherens junctions were therefore weaker in the absence of Ecad clustering, reducing cells’ ability to maintain their attachments and coordinate their movements as they attempted to undergo collective cell migration. Author René-Marc Mège thinks that modulating Ecad’s cis interactions could therefore regulate the cohesion and behavior of epithelial tissues.