Cdc42 antagonizes Rho1 activity at adherens junctions to limit epithelial cell apical tension.
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.
Warner
Stephen J
SJ
Department of Medicine, Washington University, St. Louis, MO 63110, USA.
Longmore
Gregory D
GD
D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D016764:Cell Polarity; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D004331:Drosophila melanogaster / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D019085:Fluorescent Antibody Technique, Direct; D007150:Immunohistochemistry; D008954:Models, Biological; D011493:Protein Kinase C / Q000378:metabolism; D011679:Pupa / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics
D029721:Drosophila Proteins; C115015:PKC-3 protein; D011493:Protein Kinase C; C511153:Rho1 protein, Drosophila; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins