Cdc42 targets aPKC to adherens junctions, where aPKC limits Rho activity to limit actomyosin contractility

I have read many papers talking about the signaling between Rho and Rac, but not Cdc42-Rho or Cdc42-Rac. Last week, I saw an old paper talking about Cdc42-Rac; and today, in the new issue of #JCellBiol journal, I saw an example of Cdc42-Rho.

First, I love the system they were using: mosaic analysis in fly eye. Second, it is a post-mitotic system, which elegantly takes the effect of cell division out of the discussion. Right now, there is an increased interest about the role of Cdc42 in cell division. Still debating, no solid conclusion yet, in my opinion ...

It is a very interesting paper. There are several interesting observations:

• Cdc42 DN phenotypes were in stark contrast to Cdc42 LOF clones
• depletion of Cdc42 in pupal eye epithelia did not disrupt apical–basal polarity
• Cdc42, Dlg, and Scrib were also not required for the maintenance of epithelial cell polarity in this nonproliferating epithelium
• depletion of Cdc42 led to apical cell constriction through an increase in actomyosin tension at AJs
• Cdc42 depletion resulted in increased Rho1 activity at AJs, which increased actomyosin activity
• Cdc42 regulated apical cell tension independent of the effectors Pak and Wasp, at least individually

DOI: 10.1083/jcb.200906047
The Journal of Cell Biology, Vol. 187, No. 1, 119-133
The Rockefeller University Press, 0021-9525 $30.00

Cdc42 antagonizes Rho1 activity at adherens junctions to limit epithelial cell apical tension

Stephen J. Warner 1,2 and Gregory D. Longmore 1,2

1 Department of Medicine and 2 Department of Cell Biology and Physiology, Washington University, St. Louis, MO 63110
Correspondence to Gregory D. Longmore: glongmor@dom.wustl.edu

In epithelia, cells are arranged in an orderly pattern with a defined orientation and shape. Cadherin containing apical adherens junctions (AJs) and the associated actomyosin cytoskeleton likely contribute to epithelial cell shape by providing apical tension. The Rho guanosine triphosphatases are well known regulators of cell junction formation, maintenance, and function. Specifically, Rho promotes actomyosin activity and cell contractility; however, what controls and localizes this Rho activity as epithelia remodel is unresolved. Using mosaic clonal analysis in the Drosophila melanogaster pupal eye, we find that Cdc42 is critical for limiting apical cell tension by antagonizing Rho activity at AJs. Cdc42 localizes Par6–atypical protein kinase C (aPKC) to AJs, where this complex limits Rho1 activity and thus actomyosin contractility, independent of its effects on Wiskott-Aldrich syndrome protein and p21-activated kinase. Thus, in addition to its role in the establishment and maintenance of apical–basal polarity in forming epithelia, the Cdc42–Par6–aPKC polarity complex is required to limit Rho activity at AJs and thus modulate apical tension so as to shape the final epithelium.

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