A ZO-1/?5?1-integrin complex regulates cytokinesis downstream of PKC? in NCI-H460 cells plated on fibronectin.

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 ?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/?5?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?-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, ?5-integrin and PKC? in the late stages of mammalian cell division.

SUBMITTER: Hamalisto S 

PROVIDER: S-EPMC3742740 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature