Open AccessBile canaliculi remodeling activates YAP via the actin cytoskeleton during liver regeneration
Author(s) -
Meyer Kirstin,
MoralesNavarrete Hernan,
Seifert Sarah,
WilschBraeuninger Michaela,
Dahmen Uta,
Tanaka Elly M,
Brusch Lutz,
Kalaidzidis Yannis,
Zerial Marino
Publication year - 2020
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20198985
Subject(s) - biology , microbiology and biotechnology , cytoskeleton , bone canaliculus , actin , regeneration (biology) , actin cytoskeleton , liver regeneration , actina , actin remodeling , biochemistry , anatomy , cell
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.