Contractile forces at tricellular contacts modulate epithelial organization and monolayer integrity

• Published in: Nature communications Vol. 8; no. 1; p. 13998
• Main Authors: Salomon, Julie, Gaston, Cécile, Magescas, Jérémy, Duvauchelle, Boris, Canioni, Danielle, Sengmanivong, Lucie, Mayeux, Adeline, Michaux, Grégoire, Campeotto, Florence, Lemale, Julie, Viala, Jérôme, Poirier, Françoise, Minc, Nicolas, Schmitz, Jacques, Brousse, Nicole, Ladoux, Benoit, Goulet, Olivier, Delacour, Delphine
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.01.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/107; 13/109; 13/51; 13/89; 14/19; 14/28; 14/34; 631/80/304; 631/80/79; 82/29; Actomyosin - chemistry; Actomyosin - genetics; Actomyosin - metabolism; Adolescent; Biomechanical Phenomena; Caco-2 Cells; Cell adhesion & migration; Cell Polarity; Child; Child, Preschool; Congenital diseases; Diarrhea, Infantile - genetics; Diarrhea, Infantile - metabolism; Disease; Enterocytes - chemistry; Enterocytes - metabolism; Epithelial Cell Adhesion Molecule - chemistry; Epithelial Cell Adhesion Molecule - genetics; Epithelial Cell Adhesion Molecule - metabolism; Epithelial Cells - chemistry; Epithelial Cells - cytology; Epithelial Cells - metabolism; Epithelium - chemistry; Epithelium - metabolism; Female; Gastroenterology; Humanities and Social Sciences; Humans; Infant; Malabsorption Syndromes - genetics; Malabsorption Syndromes - metabolism; Male; Membranes; Morphogenesis; multidisciplinary; Nutrition; Parenteral nutrition; Pathology; Pediatrics; Science; Science (multidisciplinary); Tight Junctions - chemistry; Tight Junctions - genetics; Tight Junctions - metabolism; France; Singapore; Paris France
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms13998

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. EpCAM is an unconventional epithelia-specific cell–cell adhesion molecule, that is mutated in the majority of cases of Congenital Tufting Enteropathy. Here the authors show that loss of EpCAM causes a concentration of contractile activity at tricellular junctions, leading to aberrant apical domain and tight junction displacement.