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Nat Commun. 2017 Jun 23;8:15839. doi: 10.1038/ncomms15839.

Ezrin enhances line tension along transcellular tunnel edges via NMIIa driven actomyosin cable formation.

Author information

1
INSERM, U1065, Université de Nice-Sophia Antipolis, Centre Méditerranéen de Médecine Moléculaire (C3M), Department of microbial toxins in host-pathogen interactions, 151 Route St Antoine de Ginestière, BP 2 3194, 06204 Nice, France.
2
Immunology Program, Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, Washington 98101, USA.
3
LCP-A2MC, Institut Jean Barriol, Université de Lorraine, 1 bd Arago, Metz 57078, France.
4
Program in Cell and Molecular Biology, Institute of Biotechnology, P.O. Box 56, University of Helsinki, Helsinki 00014, Finland.
5
Department of Biology, University of Pennsylvania, 433 S. University Avenue, Philadelphia, Pennsylvania 19104, USA.
6
Multiscale Physics-Biology-Chemistry and Cancer, Cellular Microbiology and Physics of Infection Group, Center for Infection and Immunity of Lille, CNRS UMR8204, INSERM U1019, Institut Pasteur de Lille, Centre Hospitalier Régional de Lille, Université de Lille, Lille 59021, France.
7
Multiscale Physics-Biology-Chemistry and Cancer, Laboratoire Physico Chimie Curie, Institut Curie, PSL Research University, CNRS, UMR168, Paris 75005, France.
8
Multiscale Physics-Biology-Chemistry and Cancer, Sorbonne Universités, UPMC Univ Paris 06, Paris 75005, France.
9
Equipe labellisée La Ligue contre le Cancer.

Abstract

Transendothelial cell macroaperture (TEM) tunnels control endothelium barrier function and are triggered by several toxins from pathogenic bacteria that provoke vascular leakage. Cellular dewetting theory predicted that a line tension of uncharacterized origin works at TEM boundaries to limit their widening. Here, by conducting high-resolution microscopy approaches we unveil the presence of an actomyosin cable encircling TEMs. We develop a theoretical cellular dewetting framework to interpret TEM physical parameters that are quantitatively determined by laser ablation experiments. This establishes the critical role of ezrin and non-muscle myosin II (NMII) in the progressive implementation of line tension. Mechanistically, fluorescence-recovery-after-photobleaching experiments point for the upstream role of ezrin in stabilizing actin filaments at the edges of TEMs, thereby favouring their crosslinking by NMIIa. Collectively, our findings ascribe to ezrin and NMIIa a critical function of enhancing line tension at the cell boundary surrounding the TEMs by promoting the formation of an actomyosin ring.

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