Contractile forces at tricellular contacts modulate epithelial organization and monolayer integrity

Julie Salomon, Cécile Gaston, Jérémy Magescas, Boris Duvauchelle, Danielle Canioni, Lucie Sengmanivong, Adeline Mayeux, Grégoire Michaux, Florence Campeotto, Julie Lemale, Jérôme Viala, Françoise Poirier, Nicolas Minc, Jacques Schmitz, Nicole Brousse, Benoit Ladoux, Olivier Goulet and Delphine Delacour ()
Additional contact information
Julie Salomon: Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University
Cécile Gaston: Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University
Jérémy Magescas: Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University
Boris Duvauchelle: Morphogenesis, Homoeostasis and Pathologies, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University
Danielle Canioni: Hôpital Necker-Enfants Malades, Sorbonne Paris Cité
Lucie Sengmanivong: Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie–Centre de Recherche, PSL Research University
Adeline Mayeux: Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University
Grégoire Michaux: Institut de Génétique et Développement de Rennes, CNRS UMR6290
Florence Campeotto: Hôpital Necker-Enfants Malades, Sorbonne Paris Cité
Julie Lemale: Armand-Trousseau Hospital, Assistance Publique-Hôpitaux de Paris, Institute of Cardiometabolism and Nutrition, Pierre et Marie Curie University
Jérôme Viala: Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Université Paris Diderot, Sorbonne Paris Cité, UMR843
Françoise Poirier: Morphogenesis, Homoeostasis and Pathologies, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University
Nicolas Minc: Cellular Spatial Organization, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University
Jacques Schmitz: Hôpital Necker-Enfants Malades, Sorbonne Paris Cité
Nicole Brousse: Hôpital Necker-Enfants Malades, Sorbonne Paris Cité
Benoit Ladoux: Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University
Olivier Goulet: Hôpital Necker-Enfants Malades, Sorbonne Paris Cité
Delphine Delacour: Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University

Nature Communications, 2017, vol. 8, issue 1, 1-18

Abstract: Abstract Monolayered epithelia are composed of tight cell assemblies that ensure polarized exchanges. EpCAM, an unconventional epithelial-specific cell adhesion molecule, is assumed to modulate epithelial morphogenesis in animal models, but little is known regarding its cellular functions. Inspired by the characterization of cellular defects in a rare EpCAM-related human intestinal disease, we find that the absence of EpCAM in enterocytes results in an aberrant apical domain. In the course of this pathological state, apical translocation towards tricellular contacts (TCs) occurs with striking tight junction belt displacement. These unusual cell organization and intestinal tissue defects are driven by the loss of actomyosin network homoeostasis and contractile activity clustering at TCs, yet is reversed by myosin-II inhibitor treatment. This study reveals that adequate distribution of cortical tension is crucial for individual cell organization, but also for epithelial monolayer maintenance. Our data suggest that EpCAM modulation protects against epithelial dysplasia and stabilizes human tissue architecture.

Date: 2017
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DOI: 10.1038/ncomms13998

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