Abstract
E-cadherin-catenin complex together with the cytoskeleton, builds the core of Adherens junctions (AJs). It has been reported that Scribble stabilizes the coupling of E-cadherin with catenins promoting epithelial cell adhesion, but the mechanism remains unknown. We show that Scribble, Lgl1, and NMII-A reside in a complex with 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 complexes. 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 their re-expression during EMT impedes its progression. Our results provide insight into the mechanism regulating AJ integrity by Scribble, Lgl1, and NMII-A.
Original language | American English |
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Pages (from-to) | 1-23 |
Number of pages | 23 |
Journal | Cell Adhesion and Migration |
Volume | 17 |
Issue number | 1 |
DOIs | |
State | Published - 2023 |
Bibliographical note
Funding Information:The work was supported by the Israel Cancer Association [Grant No. 20140082], Israel Science Foundation [Grant No. 745/17], and Israel Cancer Research Foundation. We thank the Pawson’s lab (Mount Sinai Hospital, Toronto, Canada) for the Lgl1 construct, Patrick Humbert and Helena Richardson (La Trobe University, Melbourne, Australia) for Scrib constructs, Robert S. Adelstein (NIH) for NMII constructs, Yinon Ben-Neria (Hebrew University) for β-catenin constructs, Cara Gottardi (Northwestern University) for GST-α-catenin, and Yael Feinstein Rotkopf for technical assistance with the microscopy work. This study was supported by the Israel Science Foundation (Grant No. 745/17), Israel Cancer Research Foundation, and Israel Cancer Association (Grant No. 20140082). S.R. holds the Daniel G. Miller Chair in Cancer Research.
Funding Information:
We thank the Pawson’s lab (Mount Sinai Hospital, Toronto, Canada) for the Lgl1 construct, Patrick Humbert and Helena Richardson (La Trobe University, Melbourne, Australia) for Scrib constructs, Robert S. Adelstein (NIH) for NMII constructs, Yinon Ben-Neria (Hebrew University) for β-catenin constructs, Cara Gottardi (Northwestern University) for GST-α-catenin, and Yael Feinstein Rotkopf for technical assistance with the microscopy work. This study was supported by the Israel Science Foundation (Grant No. 745/17), Israel Cancer Research Foundation, and Israel Cancer Association (Grant No. 20140082). S.R. holds the Daniel G. Miller Chair in Cancer Research.
Publisher Copyright:
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Keywords
- Adherens junction
- cell adhesion
- cell polarity
- EMT
- myosin
- tumor suppressor