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

Caroline Stefani (1, 2) , David Gonzalez-Rodriguez (3) , Yosuke Senju (4) , Anne Doye (1, 2) , Nadia Efimova (5) , Sébastien Janel (6, 7) , Justine Lipuma (2, 1) , Meng Chen Tsai (1, 2) , Daniel Hamaoui (1, 2) , Madhavi P. Maddugoda (2, 1) , Olivier Cochet-Escartin (8, 9) , Coline Prévost (8, 9) , Frank Lafont (6, 7) , Tatyana Svitkina (5) , Pekka Lappalainen (4) , Patricia Bassereau (8, 9) , Emmanuel Lemichez (1, 2)

1 C3M - Centre méditerranéen de médecine moléculaire
2 UNS UFR Médecine - Université Nice Sophia Antipolis - Faculté de Médecine
3 LCP-A2MC - Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes
4 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
5 University of Pennsylvania
6 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
7 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
8 SU - Sorbonne Université
9 PCC - Laboratoire Physico-Chimie Curie [Institut Curie]

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.

Domaines: Biochimie, Biologie Moléculaire

Caroline Stefani, David Gonzalez-Rodriguez, Yosuke Senju, Anne Doye, Nadia Efimova, et al.. Ezrin enhances line tension along transcellular tunnel edges via NMIIa driven actomyosin cable formation. Nature Communications, 2017, 8, pp.15839. ⟨10.1038/ncomms15839⟩. ⟨hal-01960028⟩