GSK3beta affects apical-basal polarity and cell-cell adhesion by regulating aPKC levels.
The dynamic rearrangement of cell-cell contacts is required for the establishment of functional epithelial cell sheets. However, the signaling pathways and cellular mechanisms that initiate and maintain this polarity are not well understood. We show that loss of the Wnt signaling component GSK3 beta results in increased levels of aPKC and leads to defects in apical-basal polarity. We find that GSK3 beta directly phosphorylates aPKC, which likely promotes its ubiquitin-mediated proteosomal degradation. aPKC increases the levels of Armadillo and stabilizes adherens junctions. These results suggest that the Wnt pathway component GSK3 beta regulates the polarity determinant aPKC, which in turn affects cell-cell contacts during the development of polarized tissues.
Program in Developmental Biology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Pamela F
PF
Colosimo
Xiaoping
X
Liu
Nicole A
NA
Kaplan
Nicholas S
NS
Tolwinski
D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D003433:Crosses, Genetic; D004330:Drosophila; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D047468:Immunoprecipitation; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D054875:Ubiquitination; D051153:Wnt Proteins / Q000378:metabolism / Q000502:physiology*
D051153:Wnt Proteins; D000071679:Glycogen Synthase Kinase 3 beta; C115015:PKC-3 protein; D011493:Protein Kinase C; D038362:Glycogen Synthase Kinase 3