E cadherin appears to be an essential on/off switch for initiating bile canaliculi formation

The mechanisms underlying cell polarization are fundamental in biology, yet they are not fully understood. This is particularly true for hepatocytes, which exhibit a complex polarization, enabling the formation of the bile canaliculi (BCs) network that is essential for liver excretion functions. To identify key proteins involved in hepatocyte polarization and BC formation, we performed a proteomic approach to compare the human hepatocyte cell line HepG2 to its sub clone HepG2/C3A which shows much greater efficiency in forming mature BCs. We localized LimA1 and Espin to the BC for the first time, suggesting their important role there, and confirmed the presence of NHE-RF1. Using a protein repression strategy directed against selected proteins, we highlighted the essential role of E cadherin in the initiation of BC formation. Our data showed, for the first time, that in absence of E cadherin, hepatocytes lose their ability to form BCs.