Bile canaliculi remodeling activates YAP via the actin cytoskeleton during liver regeneration


The mechanisms of organ size control remain poorly understood. A key question is how cells collectively sense the overall status of a tissue. We addressed this problem focusing on mouse liver regeneration. Using digital tissue reconstruction and quantitative image analysis, we found that the apical surface of hepatocytes forming the bile canalicular network expands concomitant with an increase in F‐actin and phospho‐myosin, to compensate an overload of bile acids. These changes are sensed by the Hippo transcriptional co‐activator YAP, which localizes to apical F‐actin‐rich regions and translocates to the nucleus in dependence of the integrity of the actin cytoskeleton. This mechanism tolerates moderate bile acid fluctuations under tissue homeostasis, but activates YAP in response to sustained bile acid overload. Using an integrated biophysical–biochemical model of bile pressure and Hippo signaling, we explained this behavior by the existence of a mechano‐sensory mechanism that activates YAP in a switch‐like manner. We propose that the apical surface of hepatocytes acts as a self‐regulatory mechano‐sensory system that responds to critical levels of bile acids as readout of tissue status.


DOI: 10.15252/msb.20198985

Projects: LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

Publication type: Not specified

Journal: Mol Syst Biol

Citation: Mol Syst Biol 16(2) : 186

Date Published: 24th Feb 2020

Registered Mode: Not specified

Authors: Kirstin Meyer, Hernan Morales‐Navarrete, Sarah Seifert, Michaela Wilsch‐Braeuninger, Uta Dahmen, Elly M Tanaka, Lutz Brusch, Yannis Kalaidzidis, Marino Zerial

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Meyer, K., Morales‐Navarrete, H., Seifert, S., Wilsch‐Braeuninger, M., Dahmen, U., Tanaka, E. M., Brusch, L., Kalaidzidis, Y., & Zerial, M. (2020). Bile canaliculi remodeling activates YAP via the actin cytoskeleton during liver regeneration. In Molecular Systems Biology (Vol. 16, Issue 2). EMBO.

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Created: 26th Feb 2020 at 19:44

Last updated: 26th Feb 2020 at 20:00

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