Research ArticleCell Biology

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

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Science Signaling  25 Feb 2020:
Vol. 13, Issue 620, eaax9940
DOI: 10.1126/scisignal.aax9940

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Adhesion signaling not required

Adherent cells position their spindle poles parallel to the plane of the substrate and orient the spindle within that plane depending on cell shape–dependent mechanical forces. Both integrins, which mediate adhesion to the extracellular matrix (ECM), and cadherins, which mediate cell-cell interactions, are implicated in establishing spindle position. Anastasiou et al. found that both cadherin- and integrin-mediated adhesion supported proper spindle positioning in cultured cells. Although adhesion-dependent integrin activation was not required to position spindles parallel to the plane of the substrate, force-dependent integrin activation at the cell cortex was required to orient the spindle in response to mechanical cues generated by adhesion topology. Thus, spindle positioning does not depend on the molecular nature of adhesion and does not specifically require integrin-based adhesion, but integrin signaling is required to transduce mechanical cues that orient the spindle.

Abstract

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.

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