RT Journal Article
SR Electronic
T1 Actomyosin Contractility Drives Bile Regurgitation as an Early Homeostatic Response to Increased Biliary Pressure in Obstructive Cholestasis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 077792
DO 10.1101/077792
A1 Kapish Gupta
A1 Qiushi Li
A1 Jun Jun Fan
A1 Eliza Li Shan Fong
A1 Ziwei Song
A1 Shupei Mo
A1 Haoyu Tang
A1 Inn Chuan Ng
A1 Chan Way Ng
A1 Pornteera Pawijit
A1 Shuangmu Zhuo
A1 Chen-Yuan Dong
A1 Boon Chuan Low
A1 Aileen Wee
A1 Yock Young Dan
A1 Pakorn Kanchanawong
A1 Peter So
A1 Virgile Viasnoff
A1 Hanry Yu
YR 2016
UL http://biorxiv.org/content/early/2016/09/28/077792.abstract
AB A wide range of liver diseases manifest as biliary obstruction, or cholestasis. However, the sequence of molecular events triggered as part of the early hepatocellular homeostatic response to abnormal elevations in biliary pressure remains poorly elucidated. Bile canaliculi are dynamic luminal structures that undergo actomyosin-mediated periodic contractions to propel secreted bile. Additionally, pericanalicular actin is accumulated during obstructive cholestasis. Therefore, we hypothesize that the pericanalicular actin cortex undergoes significant remodeling as a regulatory response against increased biliary pressure. Here, we report that, actomyosin contractility induces transient deformations along the canalicular membrane, a process we have termed inward blebbing. We show that these membrane intrusions are initiated by local ruptures in the pericanalicular actin cortex, and they typically retract following repair by actin polymerization and actomyosin contraction. However, above a certain osmotic pressure threshold, these inward blebs pinch away from the canalicular membrane into the hepatocyte cytoplasm as large vesicles (2-8 µm). Importantly, we show that these vesicles aid in the regurgitation of bile from the canalicular system. Conclusion: Actomyosin contractility induces the formation of bile-regurgitative vesicles, thus serving as an early homeostatic mechanism against increased biliary pressure during cholestasis.