Involvement of RhoA, ROCK I and myosin II in inverted orientation of epithelial polarity.

Abstract:

: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.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Yu W,Shewan AM,Brakeman P,Eastburn DJ,Datta A,Bryant DM,Fan QW,Weiss WA,Zegers MM,Mostov KE

doi

10.1038/embor.2008.135

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

923-9

issue

9

eissn

1469-221X

issn

1469-3178

pii

embor2008135

journal_volume

9

pub_type

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