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A two-tiered mechanism for stabilization and immobilization of E-cadherin

Nature volume 453, pages 751–756 (2008)Cite this article

Abstract

Epithelial tissues maintain a robust architecture which is important for their barrier function, but they are also remodelled through the reorganization of cell–cell contacts. Tissue stability requires intercellular adhesion mediated by E-cadherin, in particular its trans-association in homophilic complexes supported by actin filaments through β- and α-catenin. How α-catenin dynamic interactions between E-cadherin/β-catenin and cortical actin control both stability and remodelling of adhesion is unclear. Here we focus on Drosophila homophilic E-cadherin complexes rather than total E-cadherin, including diffusing ‘free’ E-cadherin, because these complexes are a better proxy for adhesion. We find that E-cadherin complexes partition in very stable microdomains (that is, bona fide adhesive foci which are more stable than remodelling contacts). Furthermore, we find that stability and mobility of these microdomains depend on two actin populations: small, stable actin patches concentrate at homophilic E-cadherin clusters, whereas a rapidly turning over, contractile network constrains their lateral movement by a tethering mechanism. α-Catenin controls epithelial architecture mainly through regulation of the mobility of homophilic clusters and it is largely dispensable for their stability. Uncoupling stability and mobility of E-cadherin complexes suggests that stable epithelia may remodel through the regulated mobility of very stable adhesive foci.

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Figure 1: Homophilic E-cad clusters in highly stable microdomains.
Figure 2: A stable pool of actin localizes at and stabilizes SAJs independently of α-Cat.
Figure 3: Lateral mobility of SAJs controlled by a dynamic actin network.
Figure 4: Nanoablation of cortical actin network and tethering of SAJs to actin.
Figure 5: Model of two-tiered regulation of homo-E-cad stability and mobility.

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Acknowledgements

We thank J. M. Philippe for preparing the E-cad::EosFP construct, C. Picard for contribution to the α-Cat RNAi studies, and everyone who provided us with reagents, especially H. Oda, G. Nienhaus, D. Kiehart, C. Klaembt, P. Rørth and E. Wieschaus. We also thank all members of the Lecuit and Lenne laboratories for discussions and comments on the manuscript. This work was supported by the CNRS, the Fondation Schlumberger pour l’Education et la Recherche (FSER), the ANR-Blanc together with P.-F.L.. M.C. was supported by the FSER and the Association pour la Recherche sur la Cancer (ARC). M.R. is supported by a Bourse Région PACA-Entreprise (Amplitude Systems).

Author Contributions T.L. planned the project and analysed the experiments together with M.C., M.R. and P.-F.L.; M.C. conducted the experiments except for the nano-ablations, which were performed by M.R.; P.-F.L developed the nano-ablation system together with M.R. and the data quantification procedures with M.C. The manuscript was written by T.L. and all authors commented on it.

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Authors and Affiliations

  1. Institut de Biologie du Développment de Marseille Luminy, UMR 6216 CNRS-Université de la Méditerranée, Campus de Luminy case 907, 13288 Marseille Cedex 09, France

    Matthieu Cavey, Matteo Rauzi & Thomas Lecuit

  2. Institut Fresnel, UMR 6133 CNRS-Université Paul Cézanne Aix-Marseille III, Domaine Universitaire de Saint Jérôme, 13397 Marseille Cedex 20, France

    Matteo Rauzi & Pierre-François Lenne

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  1. Matthieu Cavey
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Corresponding authors

Correspondence to Pierre-François Lenne or Thomas Lecuit.

Supplementary information

Supplementary Information

The file contains Supplementary Methods, Supplementary Figures S1-S3 with Legends and Legends to Supplementary Movies S1-S3. (PDF 1215 kb)

Supplementary Movie S1

The file contains Supplementary Movie S1. Live confocal imaging of E-cad ::GFP embryos used to measure interspot diffusion coefficients. Wild type embryo, 15-20 min after the onset of gastrulation. (MOV 4322 kb)

Supplementary Movie S2

The file contains Supplementary Movie S2. Live confocal imaging of E-cad ::GFP embryos used to measure interspot diffusion coefficients. Latrunculin-A-injected embryo, approximately 10-15 min after onset of gastrulation. (MOV 4736 kb)

Supplementary Movie S3

The file contains Supplementary Movie S3. Live confocal imaging of E-cad ::GFP embryos used to measure interspot diffusion coefficients. α-Cat RNAi-injected embryo, approx 30min after onset of gastrulation. (MOV 5171 kb)

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Cavey, M., Rauzi, M., Lenne, PF. et al. A two-tiered mechanism for stabilization and immobilization of E-cadherin. Nature 453, 751–756 (2008). https://doi.org/10.1038/nature06953

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