Involvement of RhoA, ROCK I and myosin II in inverted orientation of epithelial polarity
| Autor: | Mirjam M. P. Zegers, Qi-Wen Fan, David M. Bryant, William A. Weiss, Dennis J. Eastburn, Annette M. Shewan, Keith E. Mostov, Wei Yu, Paul Brakeman, Anirban Datta |
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| Rok vydání: | 2008 |
| Předmět: |
RHOA
Blotting Western Scientific Report Biology Transfection Biochemistry Cell Line Extracellular matrix Small hairpin RNA Cell polarity Myosin Genetics Animals Humans RNA Small Interfering Molecular Biology Rho-associated protein kinase Epithelial polarity Myosin Type II rho-Associated Kinases Reverse Transcriptase Polymerase Chain Reaction Cell Polarity Epithelial Cells Cell biology Cell culture biology.protein rhoA GTP-Binding Protein |
| Zdroj: | EMBO reports. 9:923-929 |
| ISSN: | 1469-3178 1469-221X |
| DOI: | 10.1038/embor.2008.135 |
| Popis: | In multicellular epithelial tissues, the orientation of polarity of each cell must be coordinated. Previously, we reported that for Madin-Darby canine kidney cells in three-dimensional collagen gel culture, blockade of beta1-integrin by the AIIB2 antibody or expression of dominant-negative Rac1N17 led to an inversion of polarity, such that the apical surfaces of the cells were misorientated towards the extracellular matrix. Here, we show that this process results from the activation of RhoA. Knockdown of RhoA by short hairpin RNA reverses the inverted orientation of polarity, resulting in normal cysts. Inhibition of RhoA downstream effectors, Rho kinase (ROCK I) and myosin II, has similar effects. We conclude that the RhoA-ROCK I-myosin II pathway controls the inversion of orientation of epithelial polarity caused by AIIB2 or Rac1N17. These results might be relevant to the hyperactivation of RhoA and disruption of normal polarity frequently observed in human epithelial cancers. |
| Databáze: | OpenAIRE |
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