Hepatocyte apical bulkheads provide a mechanical means to oppose bile pressure.

Autor:	Bebelman MP; Max Planck Institute of Molecular Cell Biology and Genetics , Dresden, Germany., Bovyn MJ; Max Planck Institute of Molecular Cell Biology and Genetics , Dresden, Germany.; Center for Systems Biology Dresden , Dresden, Germany.; Max Planck Institute for the Physics of Complex Systems , Dresden, Germany., Mayer CM; Max Planck Institute of Molecular Cell Biology and Genetics , Dresden, Germany., Delpierre J; Max Planck Institute of Molecular Cell Biology and Genetics , Dresden, Germany., Naumann R; Max Planck Institute of Molecular Cell Biology and Genetics , Dresden, Germany., Martins NP; Max Planck Institute of Molecular Cell Biology and Genetics , Dresden, Germany., Honigmann A; Max Planck Institute of Molecular Cell Biology and Genetics , Dresden, Germany., Kalaidzidis Y; Max Planck Institute of Molecular Cell Biology and Genetics , Dresden, Germany., Haas PA; Max Planck Institute of Molecular Cell Biology and Genetics , Dresden, Germany.; Center for Systems Biology Dresden , Dresden, Germany.; Max Planck Institute for the Physics of Complex Systems , Dresden, Germany., Zerial M; Max Planck Institute of Molecular Cell Biology and Genetics , Dresden, Germany.; Center for Systems Biology Dresden , Dresden, Germany.; Cluster of Excellence Physics of Life, Technische Universität Dresden , Dresden, Germany.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2023 Apr 03; Vol. 222 (4). Date of Electronic Publication: 2023 Jan 30.
DOI:	10.1083/jcb.202208002
Abstrakt:	Hepatocytes grow their apical surfaces anisotropically to generate a 3D network of bile canaliculi (BC). BC elongation is ensured by apical bulkheads, membrane extensions that traverse the lumen and connect juxtaposed hepatocytes. We hypothesize that apical bulkheads are mechanical elements that shape the BC lumen in liver development but also counteract elevated biliary pressure. Here, by resolving their structure using STED microscopy, we found that they are sealed by tight junction loops, connected by adherens junctions, and contain contractile actomyosin, characteristics of mechanical function. Apical bulkheads persist at high pressure upon microinjection of fluid into the BC lumen, and laser ablation demonstrated that they are under tension. A mechanical model based on ablation results revealed that apical bulkheads double the pressure BC can hold. Apical bulkhead frequency anticorrelates with BC connectivity during mouse liver development, consistent with predicted changes in biliary pressure. Our findings demonstrate that apical bulkheads are load-bearing mechanical elements that could protect the BC network against elevated pressure. (© 2023 Bebelman et al.)
Databáze:	MEDLINE
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