β‐Catenin conditional loss in hepatocytes leads to compensatory changes in tight junctions but not in desmosomal proteins

β‐Catenin a major downstream effector of the canonical Wnt pathway is also a major component of the adherens junctions (AJ), which are critical in epithelial cell biology and eventually contribute to hepatic homeostasis. Here we show that in the absence of β‐catenin in hepatocytes, using a conditional β‐catenin knockout mouse (KO), there are significant changes that occur in the tight junction (TJ), with comparatively fewer changes in desmosomes. Changes were studied by microarray and validated by protein analysis. Initially, we show that with the loss of β‐catenin there is an atypical expression of some TJ and desmosomal transcripts. In the KO livers we identify a significant decrease in TJ component claudin‐2, which is also a known target of the Wnt pathway. However, while occludin levels remain unaffected, an increase in junctional adhesion molecule‐A and claudin‐1 are evident and seem to sufficiently compensate for claudin‐2 loss and thus maintain TJ integrity. We identified loss of β‐catenin at AJ to be compensated by an increase in γ‐catenin (plakoglobin), which is a desmosomal protein. However, despite the change in transcript levels found in our microarray, protein analysis reveals no changes in any other desmosomal proteins such as desmoplakins, desmogleins, desmocollins, and plakophilins by whole‐cell lysates or cytoskeletal‐associated lysates. Thus, we have identified a novel mode of cross‐talk between AJ and TJ through Wnt/β‐catenin/claudin axis. Therefore, desmosomes do not appear to be the source of γ‐catenin that compensates for β‐catenin loss at AJ, since no compensatory changes in desmosomal protein expression are observed.