Molecular Bases of Cell-Cell Junctions Stability and Dynamics

Abstract

Epithelial cell -cell junctions are formed by apical adherens junctions (AJs), which are composed of cadherin adhesion molecules interacting in a dynamic way with the cortical actin cytoskeleton. Regulation of cell-cell junction stability and dynamics is crucial to maintain tissue integrity and allow tissue remodeling throughout development. Actin filament turnover and organization are tightly controlled together with myosin-II activity to produce mechanical forces that drive the assembly, maintenance, and remodeling of AJs. In this review, we will discuss these three distinct stages in the lifespan of cell -cell junctions, using several developmental contexts, which illustrate how mechanical forces are generated and transmitted at junctions, and how they impact on the integrity and the remodeling of cell -cell junctions.

Controlled levels of canonical Wnt signaling are required for neural crest migration

“…Initially, exploring cells use large protrusions to scan the surrounding for potential binding partners. Establishing a cell-cell contact results in accumulation of cadherins at the contact point, which bind adjacent cells together through calcium-dependent heomophilic interactions (Cavey and Lecuit, 2009;Meng and Takeichi, 2009). During the initial step of exploration, at the very first moment of contact cells exhibit a transient peak of Rac1 activity allowing for further exploration, which is immediately inhibited by activation of RhoA upon formation of adherents junctions (Perez et al, 2008).…”

“…Initial contact sites are regarded as footholds for lateral expansion of adherent junctions, which occurs outward in alternated rounds of activation and inhibition of Rac1 and RhoA activities. Subsequently myosin-mediated tension pulling inward on the contacts sites mechanically facilitates expansion of adherent junctions (Cavey and Lecuit, 2009). …”

Small Rho GTPase-mediated actin dynamics at endothelial adherens junctions

“…This homophilic ligation of cadherins triggers actin cytoskeleton rearrangements, driving contact expansion and stabilization. 31 Thus, there is bidirectional interplay, and cadherin ligation has been demonstrated to recruit several actin regulators, including Rac1, Cdc42, Arp2/3, cortactin, N-WASP and Ena/VASP. 32-36 37-40 Actin-driven membrane protrusions are not only required for nascent cell-cell junction formation, but are also described to be important for maintenance of integrity of mature junctions.…”

Chibby1 knockdown promotes mesenchymal-to-epithelial transition-like changes

“…31,32 The cytoplasmic domain of E-cadherin binds b-catenin at adherens junctions, which in turn interacts with a-catenin to link the complex to the actin cytoskeleton. Since Cby1 was initially isolated as a b-catenin-binding protein, 13 we analyzed the expression of b-catenin and E-cadherin in Cby1-K D cells.…”

“…Assembly of E-cadherin-mediated adherens junctions is thought to initialize the establishment of cell-cell contacts, triggering the subsequent formation of other cell-cell junctions. 31,32 We therefore investigated if tight junctions are also affected in Cby1-K D cells by IF staining for ZO-1, a widely used tight junction marker. As shown in Fig.…”