Adherens junctions stimulate and spatially guide integrin activation and extracellular matrix deposition.

Cadherins and integrins are intrinsically linked through the actin cytoskeleton and are largely responsible for the mechanical integrity and organization of tissues. We show that cadherin clustering stimulates and spatially guides integrin activation. Adherens junction (AJ)-associated integrin activation depends on locally generated tension and does not require extracellular matrix ligands. It leads to the creation of primed integrin clusters, which spatially determine where focal adhesions will form if ligands are present and where ligands will be deposited. AJs that display integrin activation are targeted by microtubules facilitating their disassembly via caveolin-based endocytosis, showing that integrin activation impacts the stability of the core cadherin complex. Thus, the interplay between cadherins and integrins is more intimate than what was once believed and is rooted in the capacity of active integrins to be stabilized via AJ-generated tension. Altogether, our data establish a mechanism of cross-regulation between cadherins and integrins.

Mitotic cell responses to substrate topological cues are independent of the molecular nature of adhesion.

Correct selection of the cell division axis is important for cell differentiation, tissue and organ morphogenesis, and homeostasis. Both integrins, which mediate interactions with extracellular matrix (ECM) components such as fibronectin, and cadherins, which mediate interactions between cells, are implicated in the determination of spindle orientation. We found that both cadherin- and integrin-based adhesion resulted in cell divisions parallel to the attachment plane and elicited identical spindle responses to spatial adhesive cues. This suggests that adhesion topology provides purely mechanical spatial cues that are independent of the molecular nature of the interaction or signaling from adhesion complexes. We also demonstrated that cortical integrin activation was indispensable for correct spindle orientation on both cadherin and fibronectin substrates. These data suggest that spindle orientation responses to adhesion topology are primarily a result of force anisotropy on the cell cortex and show that integrins play a central role in this process that is distinct from their role in cell-ECM interactions.