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Cdc42 antagonizes Rho1 activity at adherens junctions to limit epithelial cell apical tension
Correspondence to Gregory D. Longmore: glongmor{at}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.
Abbreviations used in this paper: AJ, adherens junction; APF, after puparium formation; aPKC, atypical PKC; Baz, Bazooka; CAT, catalytic domain; Crbs, Crumbs; DE-cadherin, Drosophila epithelial cadherin; Dia, Diaphanous; Dlg, Discs large; DN, dominant negative; Flp, flippase; GAP, GTPase-activating protein; GEF, guanine nucleotide exchange factor; GMR, glass multimer reporter; hsFLP, heat shock Flp; LOF, loss-of-function; MARCM, mosaic analysis with a repressible cell marker; MLC, myosin light chain; MRCK, myotonic dystrophy kinase-related Cdc42-binding kinase; Mtl, Mig-2 like; Pak, p21-activated kinase; PEC, pigment epithelial cell; Rok, Rho-associated kinase; Scrib, Scribble; SJ, septate junction; Ssh, slingshot; Tsr, twinstar; UAS, upstream activating sequence; Wsp, Wiskott-Aldrich syndrome protein; WT, wild type.
© 2009 Warner and Longmore
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
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