title: Hepatocyte γ-catenin compensates for conditionally deleted β-catenin at adherens junctions.
abstract: OBJECTIVE
  Wnt/β-catenin signaling is important in liver physiology. Moreover, β-catenin is also pivotal in adherens junctions (AJ). Here, we investigate hepatocyte-specific β-catenin conditional null mice (KO) for any alterations in AJ and related tight junctions (TJ).
  
  
  METHODS
  Using gene array, PCR, Western blot, immunohistochemistry, immunofluorescence, and co-immunoprecipitation, we compare and contrast the composition of AJ and TJ in KO and littermate wild-type (WT) control livers.
  
  
  RESULTS
  We show association of E-cadherin with β-catenin in epithelial cells of WT livers, which is lost in the KOs. While total levels of α-catenin, E-cadherin, and F-actin were modestly decreased, KO livers show increased γ-catenin/plakoglobin. By co-immunoprecipitation, E-cadherin/β-catenin/F-actin association was observed in WT livers, while the association of E-cadherin/γ-catenin/F-actin was evident in KO livers. γ-Catenin was localized at the hepatocyte membrane at baseline in the KO liver. While γ-catenin gene expression remained unaltered, an increase in serine- and threonine-phosphorylated, but not tyrosine-phosphorylated γ-catenin was observed in KO livers. A continued presence of γ-catenin at the hepatocyte membrane, without any nuclear localization, was observed in liver regeneration after partial hepatectomy at 40 and 72 h, in both KO and WT. Analysis of TJ revealed lack of claudin-2 and increased levels of JAM-A and claudin-1 in KO livers.
  
  
  CONCLUSIONS
  β-Catenin adequately maintains AJ in the absence of β-catenin in hepatocytes; however, it lacks nuclear localization. Moreover, β-catenin/claudin-2 may be an important mechanism of crosstalk between the AJ and TJ.
authors.affiliation: Department of Pathology, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Emily Diane
authors.initials: ED
authors.lastname: Wickline
authors.forename: Prince Kwaku
authors.initials: PK
authors.lastname: Awuah
authors.forename: Jaideep
authors.initials: J
authors.lastname: Behari
authors.forename: Mark
authors.initials: M
authors.lastname: Ross
authors.forename: Donna B
authors.initials: DB
authors.lastname: Stolz
authors.forename: Satdarshan P S
authors.initials: SP
authors.lastname: Monga
mesh_terms: D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019108:Tight Junctions / Q000378:metabolism; D051176:beta Catenin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051185:gamma Catenin / Q000378:metabolism*
chemical_list: D000199:Actins; D015820:Cadherins; C495293:Jup protein, mouse; D012333:RNA, Messenger; D051176:beta Catenin; D051185:gamma Catenin