Dual ablation of β- and γ-catenin: Critical regulators of junctions and their functions

Abstract

The duality of β- and γ–catenin during liver injury has not been defined. It’s well known that loss of β-catenin plays a critical role in overall liver health and is a major component of adherens junctions (AJ). Further, γ-catenin has been shown to regulate β-catenin and vice-versa. In this excellent manuscript, the authors investigated the effects of knocking out both β- and γ–catenin creating a β-;γ-catenin-double knockout (DKO). The result of this interbreeding revealed a model that is reminiscent of early childhood cholestatic liver diseases (CLD) like Progressive Familial Intrahepatic Cholestasis (PFIC). The authors provide both in vivo and in vitro data to demonstrate the important role of these catenin genes in the regulation of hepatocyte-junctions. The experiments show partially redundant function of catenin’s at hepatocyte AJ in regulating tight junctions (TJ) and contributing to a disrupted blood-bile barrier. Further, concomitant hepatic loss of β- and γ-catenin disrupts structural and functional integrity of AJ and TJ via transcriptional and posttranslational mechanisms. Overall, these studies shed important light on junctional protein dysregulation during CLD.