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

Maha Abedrabbo; Shirel Sloomy; Reham Abu-Leil; Einav Kfir-Cohen; Shoshana Ravid

doi:10.1080/19336918.2023.2260645

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

Maha Abedrabbo, Shirel Sloomy, Reham Abu-Leil, Einav Kfir-Cohen, Shoshana Ravid^*

^*Corresponding author for this work

Department of Biochemistry and Molecular Biology

Research output: Contribution to journal › Article › peer-review

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
Pages (from-to)	1-23
Number of pages	23
Journal	Cell Adhesion and Migration
Volume	17
Issue number	1
DOIs	https://doi.org/10.1080/19336918.2023.2260645
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

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10.1080/19336918.2023.2260645

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

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.",

keywords = "Adherens junction, cell adhesion, cell polarity, EMT, myosin, tumor suppressor",

author = "Maha Abedrabbo and Shirel Sloomy and Reham Abu-Leil and Einav Kfir-Cohen and Shoshana Ravid",

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{\textquoteright}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{\textquoteright}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: {\textcopyright} 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",

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doi = "10.1080/19336918.2023.2260645",

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AU - Kfir-Cohen, Einav

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N1 - 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.

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N2 - 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.

AB - 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.

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ER -

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

Abstract

Bibliographical note

Keywords

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