Cortactin Scaffolds Arp2/3 and WAVE2 at the Epithelial Zonula Adherens

Abstract

Background: Productive epithelial interactions require actin filament assembly at E-cadherin adhesions. Results: Cortactin localizes to the zonula adherens through interactions with E-cadherin and N-WASP; there it recruits Arp2/3 and WAVE2 by separate mechanisms to support actin nucleation. Conclusion: Cortactin acts as a coincident scaffold. Significance: Cortactin can regulate the dynamic integration of cadherin adhesion with the actin cytoskeleton.

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

“…It is likely that Arp2/3-dependent nucleation is favoured at cell-cell contact via different strategies: (i) distinct regulation by partners such as N-WASP [27] or cortactin, which provides a scaffold for Arp complexes at junctions [28] or (ii) inhibition of branching activity by -catenin [29][30][31] or EPLIN, a cross-linking protein [32]. Alternatively, the precise regulation of profilin, a G-actin binding protein, may determine the preferential incorporation of monomers to filaments nucleated by formins instead of Arp2/3 [33].…”

Cortactin is a scaffolding platform for the E-cadherin adhesion complex and is regulated by protein kinase D1 phosphorylation

“…S1A). Actin accumulation and F-actin binding of cortactin are important features that determine the role of cortactin at adherens junctions (Han et al, 2014). To evaluate PKD1-mediated cell-cell adhesion phenotypes in the context of these factors, we also performed aggregation assays using a cortactin-W22A mutant, Hanging droplet cell-cell adhesion assays with Caco-2 cells following stable knockdown of cortactin (sh cortactin).…”

Active contractility at E-cadherin junctions and its implications for cell extrusion in cancer

“…Thus actin stabilization represents an independent mechanism to modulate contractile stress at cadherin junctions. How it cooperates with the other determinants of junctional contractility 21,29 will be an interesting question for future research.…”