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bioRxiv · 10.1101/2023.02.15.528619

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

Abedrabbo, M.·Sloomi, S.·Abu-leil, R.·Cohen-Kfir, E.·Ravid, S.
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Abstract

E-cadherin, - and {beta}-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. aPKC{zeta} 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 TGF{beta}-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.

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Abedrabbo, M., Sloomi, S., Abu-leil, R., Cohen-Kfir, E., Ravid, S.. 2023-02-15. Scribble, Lgl1, and myosin IIA interact with α/β-catenin to maintain epithelial junction integrity. https://doi.org/10.1101/2023.02.15.528619

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