A ZO-1/alpha 5 beta 1-Integrin Complex Regulates Cytokinesis Downstream of PKC epsilon in NCI-H460 Cells Plated on Fibronectin

: Hamalisto S, Pouwels J, de Franceschi N, Saari M, Ivarsson Y, Zimmermann P, Brech A, Stenmark H, Ivaska J

Publisher: PUBLIC LIBRARY SCIENCE

: 2013

: PLoS ONE

: PLOS ONE

: ARTN e70696

: 8

: 9

: 1932-6203

DOI: https://doi.org/10.1371/journal.pone.0070696

: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742740/

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 alpha 5-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/alpha 5 beta 1-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 PKC epsilon-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, alpha 5-integrin and PKC epsilon in the late stages of mammalian cell division.