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

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...

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Detalles Bibliográficos
Autores principales: Stefani, Caroline, Gonzalez-Rodriguez, David, Senju, Yosuke, Doye, Anne, Efimova, Nadia, Janel, Sébastien, Lipuma, Justine, Tsai, Meng Chen, Hamaoui, Daniel, Maddugoda, Madhavi P., Cochet-Escartin, Olivier, Prévost, Coline, Lafont, Frank, Svitkina, Tatyana, Lappalainen, Pekka, Bassereau, Patricia, Lemichez, Emmanuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490010/
https://www.ncbi.nlm.nih.gov/pubmed/28643776
http://dx.doi.org/10.1038/ncomms15839
Descripción
Sumario: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.