Scribble, Lgl1, and myosin IIA interact with α/β-catenin to maintain epithelial junction integrity

Abstract

AbstractE-cadherin, α- and β-catenin (E-cadherin-catenin complex) together with the cytoskeleton build the core of Adherens junctions (AJs). Scribble and Lgl1 are tumor suppressors, and it has been reported that Scribble stabilizes the coupling of E-cadherin with catenins promoting epithelial cell adhesion, but the molecular mechanism remains unknown. Here, we investigated the role of Scribble, Lgl1, and myosin-IIA (NMII-A) in AJ integrity. We show that Scribble, Lgl1, and NMII-A reside in a complex with the E-cadherin-catenin complex. Depletion of either Scribble or Lgl1 disrupts the localization of E-cadherin-catenin complex to AJs. aPKCζ phosphorylation of Lgl1 regulates AJ localization of Lgl1 and E-cadherin-catenin complex. Both Scribble and Lgl1 regulate the activation and recruitment of NMII-A at AJs. Finally, Scribble and Lgl1 are downregulated by TGFβ-induced EMT, and re-expression of Scribble or Lgl1 during EMT impedes its progression. Our results provide insight into the mechanism regulating AJ integrity by Scribble, Lgl1, and NMII-A.