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Involvement of RhoA, ROCK I and myosin II in inverted orientation of epithelial polarity
Author(s) -
Yu Wei,
Shewan Annette M,
Brakeman Paul,
Eastburn Dennis J,
Datta Anirban,
Bryant David M,
Fan QiWen,
Weiss William A,
Zegers Mirjam M P,
Mostov Keith E
Publication year - 2008
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2008.135
Subject(s) - rhoa , cell polarity , microbiology and biotechnology , myosin , polarity (international relations) , myosin light chain kinase , rho associated protein kinase , biology , chemistry , biophysics , signal transduction , cell , biochemistry
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 β1‐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.