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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http://dx.doi.org/10.1080/19336918.2023.2260645 | DOI Listing |
Cell Adh Migr
December 2023
Department of Biochemistry and Molecular Biology, The Institute of Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
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.
View Article and Find Full Text PDFGenetics
December 2021
Division of Developmental Biology, Department of Biology, Faculty of Science, Institute of Biodynamics and Biocomplexity, Utrecht University, 3584 CH Utrecht, the Netherlands.
Interactions among proteins are fundamental for life and determining whether two particular proteins physically interact can be essential for fully understanding a protein's function. We present Caenorhabditis elegans light-induced coclustering (CeLINC), an optical binary protein-protein interaction assay to determine whether two proteins interact in vivo. Based on CRY2/CIB1 light-dependent oligomerization, CeLINC can rapidly and unambiguously identify protein-protein interactions between pairs of fluorescently tagged proteins.
View Article and Find Full Text PDFMol Biol Cell
September 2020
Department of Biochemistry and Molecular Biology, The Institute of Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Scribble (Scrib) and Lethal giant larvae 1 (Lgl1) are conserved polarity proteins that play important roles in different forms of cell polarity. The roles of Scrib and Lgl1 in apical-basal cell polarity have been studied extensively, but little is known about their roles in the cell polarity of migrating cells. Furthermore, the effect of Scrib and Lgl1 interaction on cell polarity is largely unknown.
View Article and Find Full Text PDFNat Commun
November 2013
Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia.
The production of protective antibody requires effective signalling of naive B cells following encounter with antigen, and the divergence of responding B lymphocytes into distinct lineages. Polarity proteins have recently been proposed as important mediators of both the initial B cell response, and potentially of asymmetric cell division. Here we show that, although polarity proteins of the Scribble complex, Scribble, Dlg1 and Lgl1, are expressed and polarized during early B cell activation, their deficiency has no effect on the in vivo outcome of immunization or challenge with influenza infection.
View Article and Find Full Text PDFHistochem Cell Biol
September 2011
Department of Pathology and Cell Biology, Université de Montréal, Canada.
Wild-type (WT) and myosin heavy chain IIB null [MHCIIB (-/-)] embryonic fibroblasts were used as an experimental model to assess the role of the isoform B of myosin II (MII) in the regulation of the cell shape and intrinsic polarity. Genetic ablation of MHCIIB causes a persistent albeit, unstable protrusive activity in embryonic fibroblasts (Lo et al. in Nonmuscle myosin IIB is involved in the guidance of fibroblast migration.
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