title: E-cadherin supports steady-state Rho signaling at the epithelial zonula adherens.
abstract: In simple polarized epithelial cells, the Rho GTPase commonly localizes to E-cadherin-based cell-cell junctions, such as the zonula adherens (ZA), where it regulates the actomyosin cytoskeleton to support junctional integrity and tension. An important question is how E-cadherin contributes to Rho signaling, notably whether junctional Rho may depend on cadherin adhesion. We sought to investigate this by assessing Rho localization and activity in epithelial monolayers depleted of E-cadherin by RNAi. We report that E-cadherin depletion reduced both Rho and Rho-GTP at the ZA, an effect that was rescued by expressing a RNAi-resistant full-length E-cadherin transgene. This impact on Rho signaling was accompanied by reduced junctional localization of the Rho GEF ECT2 and the centralspindlin complex that recruits ECT2. Further, the Rho signaling pathway contributes to the selective stabilization of E-cadherin molecules in the apical zone of the cells compared with E-cadherin at the lateral surface, thereby creating a more defined and restricted pool of E-cadherin that forms the ZA. Thus, E-cadherin and Rho signaling cooperate to ensure proper ZA architecture and function.
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia.
authors: Rashmi
authors: R
authors: Priya
authors: Alpha S
authors: AS
authors: Yap
authors: Guillermo A
authors: GA
authors: Gomez
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D015820:Cadherins; D018797:Cell Cycle Proteins; C489850:ECT2 protein, human; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; C104434:spindlin; D024462:Myosin Type II; D020742:rhoA GTP-Binding Protein
keywords: CS; Centralspindlin; E-cad; E-cadherin; ECT2; IIA; KD; Myosin II; Rho; ZA; Zonula adherens; centralspindlin; knockdown; myosin IIA; zonula adherens