A two-tiered mechanism for stabilization and immobilization of E-cadherin

Abstract

Epithelial tissues maintain a robust architecture which is important for their barrier function, but they are also remodelled through the reorganization of cell-cell contacts. Tissue stability requires intercellular adhesion mediated by E-cadherin, in particular its trans-association in homophilic complexes supported by actin filaments through beta- and alpha-catenin. How alpha-catenin dynamic interactions between E-cadherin/beta-catenin and cortical actin control both stability and remodelling of adhesion is unclear. Here we focus on Drosophila homophilic E-cadherin complexes rather than total E-cadherin, including diffusing 'free' E-cadherin, because these complexes are a better proxy for adhesion. We find that E-cadherin complexes partition in very stable microdomains (that is, bona fide adhesive foci which are more stable than remodelling contacts). Furthermore, we find that stability and mobility of these microdomains depend on two actin populations: small, stable actin patches concentrate at homophilic E-cadherin clusters, whereas a rapidly turning over, contractile network constrains their lateral movement by a tethering mechanism. alpha-Catenin controls epithelial architecture mainly through regulation of the mobility of homophilic clusters and it is largely dispensable for their stability. Uncoupling stability and mobility of E-cadherin complexes suggests that stable epithelia may remodel through the regulated mobility of very stable adhesive foci.

EMT, the cytoskeleton, and cancer cell invasion

“…Thus, the formation of E-cadherinmediated cell-cell adhesion fundamentally modulates the organization of cytoskeleton. This classical view of a direct connection between the E-cadherin/β-catenin/α-catenin complex and the actin network has been challenged by recent studies demonstrating that a reconstructed cadherincatenin complex fails to bind actin filaments in vitro [24], and that E-cadherin, localized in electron-dense microdomains called spot adherens junctions (SAJs), binds to actin in an α-catenin-independent manner [25]. Here, the authors describe a model in which two distinct actin populations are involved in the zonula adherens architecture (Fig.…”

Nanodomains in Biomembranes with Recycling

“…For example, the observation of nano-domains of rhodopsin (a GPCR) in cadavers' retina cells [8], very similar to those observed in fixed cells or membrane sheets, suggests that active processes are not essential. Alternatively, some other works propose that out-of-equilibrium mechanisms are necessarily at play, driven by active membrane recycling [25,29,14,30,31,26,32]. We explored whether both approaches could be discriminated from an experimental perspective.…”

“…[ 14 ] and to G(ñ) − G(n * ) G (n * )(ñ − n * ) + 1/2 G (n * )(ñ − n * ) 2 , we obtain the simple relation ln K n * 1 2 G (n * )(ñ − n * ) 2 .…”

“…There is no reason to anticipate that they arrive in clusters as large as those observed on the membrane and we assume for simplicity sake that they are principally carried as monomers, as in Refs. [14,32]. Conversely, endocytosis and related processes remove material from the membrane.…”

“…For example, the MOR-GPCR was examined by particle-tracking and was found to be locally confined in nano-domains, presumably because of inter-protein longrange forces [13]. E-cadherins constitute another example for which nano-patterning of the membrane has been shown to be involved in its biological function, clusters serving as adhesive foci in adherens junctions [14,15]. Grouping identical receptors in a same cluster can also optimize and make more reliable their response to external stimuli [6,8,16,17,19].…”