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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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Published in: | PloS one 2013, Vol.8 (8), p.e70696-e70696 |
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description | 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. |
doi_str_mv | 10.1371/journal.pone.0070696 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0070696</identifier><identifier>PMID: 23967087</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2013, Vol.8 (8), p.e70696-e70696</ispartof><rights>2013 Hämälistö et al. 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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. 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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. 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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 |
title | A ZO-1/α5β1-integrin complex regulates cytokinesis downstream of PKCε in NCI-H460 cells plated on fibronectin |
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