A ZO-1/α5β1-integrin complex regulates cytokinesis downstream of PKCε in NCI-H460 cells plated on fibronectin

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. Th...

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Bibliographic Details
Published in:PloS one 2013, Vol.8 (8), p.e70696-e70696
Main Authors: Hämälistö, Saara, Pouwels, Jeroen, de Franceschi, Nicola, Saari, Markku, Ivarsson, Ylva, Zimmermann, Pascale, Brech, Andreas, Stenmark, Harald, Ivaska, Johanna
Format: Article
Language:English
Subjects:
Actin
Adherent cells
Biology
Biotechnology
Cell Adhesion
Cell adhesion & migration
Cell Culture Techniques
Cell cycle
Cell division
Cell Line, Tumor
Cells, Cultured
Cleavage
Cytokinesis
Extracellular matrix
Fibroblasts
Fibronectin
Fibronectins - metabolism
Gene expression
Humans
Immunoglobulins
Integrin alpha5beta1 - metabolism
Integrins
Kinases
Localization
Lung cancer
Microscopy
Models, Biological
Phosphatidylinositol 4,5-Diphosphate - metabolism
Phosphorylation
Protein Binding
Protein kinase C
Protein Kinase C-epsilon - metabolism
Proteins
Recruitment
Signal Transduction
Zonula occludens-1 protein
Zonula Occludens-1 Protein - metabolism
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0070696