puc-header

Distinct Actin-Dependent Nanoscale Assemblies Underlie the Dynamic and Hierarchical Organization of E-Cadherin

57 Pages Posted: 2 Dec 2019 Publication Status: Review Complete

See all articles by Rumamol Chandran

Rumamol Chandran

Tata Institute of Fundamental Research (TIFR) - National Centre for Biological Sciences (TIFR)

Girish Kale

Tata Institute of Fundamental Research (TIFR) - National Centre for Biological Sciences (TIFR)

Jean-Marc Philippe

Aix-Marseille University - Turing Center for Living Systems

Thomas Lecuit

Aix-Marseille University - Turing Center for Living Systems; Université Paris I Panthéon-Sorbonne - College of France

Satyajit Mayor

Tata Institute of Fundamental Research (TIFR) - Department of Cellular Organization and Signaling

More...

Abstract

Intercellular adhesion mediated by E-cadherin is pivotal in maintaining epithelial tissue integrity and for tissue morphogenesis. Adhesion requires homophilic interactions between extracellular domains of E-cadherin molecules from neighboring cells. The interaction of its cytoplasmic domains with the cortical acto-myosin network, appears to strengthen adhesion, although, it is unclear how cortical actin affects the organization and function of E-cadherin dynamically. Here we use the ectopic expression of Drosophila E-cadherin (E-cad) in larval hemocytes, which lack endogenous E-cad, to recapitulate functional cell-cell junctions in a convenient model system. We used fluorescence emission anisotropy-based microscopy and Fluorescence Correlation Spectroscopy (FCS) to probe the nanoscale organization of E-cad. We find that E-cad at cell-cell junctions in hemocytes exhibits a clustered trans-paired organization, similar to that reported for the adherens junction in the developing embryonic epithelial tissue. Further, we find that extra-junctional E-cad is also organized as relatively immobile nanoclusters as well as diffusive and more loosely packed oligomers and monomers. These oligomers are promoted by cis­-interactions of the ectodomain and, strikingly, their growth is constantly counteracted by cortical actomyosin. Oligomers in turn assist in generating nanoclusters that are stabilized by cortical acto-myosin. Thus, actin remodels oligomers and stabilizes nanoclusters, revealing a requirement for actin in the dynamic organization of E-cad at the nanoscale. This dynamic organization is also present at cell-cell contacts (junction), and its disruption affects junctional integrity in the hemocyte system, as well as in the embryo. Our observations uncover a hierarchical mechanism for the nanoscale organization of E-cad, which is necessary for dynamic adhesion and maintaining junctional integrity in the face of extensive remodeling.

Keywords: E-cadherin, nano-scale organization, Drosophila, emission anisotropy, fluorescence correlation spectroscopy

Suggested Citation

Chandran, Rumamol and Kale, Girish and Philippe, Jean-Marc and Lecuit, Thomas and Mayor, Satyajit, Distinct Actin-Dependent Nanoscale Assemblies Underlie the Dynamic and Hierarchical Organization of E-Cadherin (November 26, 2019). Available at SSRN: https://ssrn.com/abstract=3493379 or http://dx.doi.org/10.2139/ssrn.3493379
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Rumamol Chandran

Tata Institute of Fundamental Research (TIFR) - National Centre for Biological Sciences (TIFR)

Bangalore
India

Girish Kale

Tata Institute of Fundamental Research (TIFR) - National Centre for Biological Sciences (TIFR)

Bangalore
India

Jean-Marc Philippe

Aix-Marseille University - Turing Center for Living Systems

3 Avenue Robert Schuman
Aix-en-Provence, 13628
France

Thomas Lecuit

Aix-Marseille University - Turing Center for Living Systems ( email )

3 Avenue Robert Schuman
Aix-en-Provence, 13628
France

Université Paris I Panthéon-Sorbonne - College of France ( email )

11, place Marcelin Berthelot
75231 Paris Cedex 05
France

Satyajit Mayor (Contact Author)

Tata Institute of Fundamental Research (TIFR) - Department of Cellular Organization and Signaling

STCS, TIFR, 1, Homi Bhabha Road
Colaba
Mumbai, 400005
India

Click here to go to Cell.com

Paper statistics

Abstract Views
186
Downloads
4