The Adherens Junction: A Mosaic of Cadherin and Nectin Clusters Bundled by Actin Filaments

Abstract

Summary Cadherin and nectin are distinct transmembrane proteins of adherens junctions. Their ectodomains mediate adhesion while their cytosolic regions couple the adhesive contact to the cytoskeleton. Both these proteins are essential for adherens junction formation and maintenance. However, some basic aspects of these proteins, such as their organization in adherence junctions, have remained open. Therefore, using super-resolution microscopy and live-imaging, we focused on the subjunctional distribution of these proteins. We showed that cadherin and nectin in the junctions of A431 cells and human keratinocytes are located in separate clusters. The size of each cluster is independent of that of the adjacent clusters and can significantly fluctuate over time. Several nectin and cadherin clusters that constitute an individual adherens junction are united by the same actin filament bundle. Surprisingly, interactions between each cluster and F-actin are not uniform since neither vinculin nor LIM domain actin-binding proteins match the boundaries of cadherin or nectin clusters. Thus, the adherens junction is not a uniform structure but a mosaic of different adhesive units with very diverse modes of interaction with the cytoskeleton. We propose that such a mosaic architecture of adherence junctions is important for the fast regulation of their dynamics.

Cadherin controls nectin recruitment into adherens junctions by remodeling the actin cytoskeleton

“…As we have shown previously, these cells form typical adherens junctions consisting of cadherin (E-and P-cadherins) and nectin-2 clusters (Indra et al, 2013). We have also shown that once these cells touch one another, cadherin and nectin clusters always appear at the same sites (Indra et al, 2014).…”

“…S2A). As in many other cell types (Indra et al, 2013), the nectin-containing adherens junctions were also positive for vinculin (Fig. 1D).…”

“…These two receptors are key components of adherens junctions, where they form separate but closely associated adhesive clusters interconnected by an actin bundle (Takai et al, 2008;Indra et al, 2013). It has been suggested that cadherin and nectin co-recruitment into adherens junctions is under the control of nectin.…”

“…These proteins can form junctions independently from one another; nectin junctions assemble in cadherin-deficient cells , and cadherin junctions are formed, albeit with reduced kinetics, in nectin-inactivated cells (Sato et al, 2006;Tanaka-Okamoto et al, 2011;Indra et al, 2014). In adherens junctions, cadherin and nectin are located in separate, yet closely associated, adhesive clusters (Indra et al, 2013). How these two different and independent adhesion receptors are co-recruited into the same adhesive structure is not yet known.…”

Spatial integration of E-cadherin adhesion, signalling and the epithelial cytoskeleton

“…via catenins) and other transmembrane proteins (i.e. nectins [17], growth factors receptors and integrins). In spite of extensive progress in the identification of cytoskeletal proteins found at junctions [18,19], the precise F-actin organization and the specific actin remodelling functions at cadherin contacts lack in-depth understanding.…”