A ZO-1/α5β1-Integrin Complex Regulates Cytokinesis Downstream of PKCε in NCI-H460 Cells Plated on Fibronectin

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Abstract

Recently, we demonstrated that integrin adhesion to the extracellular matrix at the cleavage furrow is essential for cytokinesis of adherent cells. Here, we report that tight junction protein ZO-1 (Zonula Occludens-1) is required for successful cytokinesis in NCI-H460 cells plated on fibronectin. This function of ZO-1 involves interaction with the cytoplasmic domain of α5-integrin to facilitate recruitment of active fibronectin-binding integrins to the base of the cleavage furrow. In the absence of ZO-1, or a functional ZO-1/α5β1-integrin complex, proper actin-dependent constriction between daughter cells is impaired and cells fail cytokinesis. Super-resolution microscopy reveals that in ZO-1 depleted cells the furrow becomes delocalized from the matrix. We also show that PKCε-dependent phosphorylation at Serine168 is required for ZO-1 localization to the furrow and successful cell division. Altogether, our results identify a novel regulatory pathway involving the interplay between ZO-1, α5-integrin and PKCε in the late stages of mammalian cell division. © 2013 Hämälistö et al.

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Hämälistö, S., Pouwels, J., de Franceschi, N., Saari, M., Ivarsson, Y., Zimmermann, P., … Ivaska, J. (2013). A ZO-1/α5β1-Integrin Complex Regulates Cytokinesis Downstream of PKCε in NCI-H460 Cells Plated on Fibronectin. PLoS ONE, 8(8). https://doi.org/10.1371/journal.pone.0070696

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