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δ‐Catenin: A new member of the GSK‐3β signaling complex that promotes β‐catenin turnover
Author(s) -
Bareiss Sonja Karin,
Lu Qun
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.25
Subject(s) - catenin , immunoprecipitation , ubiquitin , phosphorylation , microbiology and biotechnology , colocalization , chemistry , beta catenin , signal transduction , proteasome , ubiquitin ligase , biology , wnt signaling pathway , biochemistry , gene
Through a multiprotein complex, GSK‐3 β phosphorylates and destabilizes β ‐catenin, a key element for neuronal functions. δ ‐Catenin, a neuronal specific member of the β ‐catenin family, is involved in dendrogenesis and its expression is critical for cognitive function. However, mechanisms regulating δ‐catenin expression are poorly understood. We investigated if δ‐catenin expression may be regulated by GSK‐3β and thereby participate in the complex regulating β ‐catenin turnover. We show that GSK‐3 β immunoprecipitates with and phosphorylates δ‐catenin. Immunofluorescent microscopy revealed colocalization of δ‐catenin with GSK‐3 β and β ‐catenin in the dendrites. Treatment of neurons with a GSK‐3 β inhibitor resulted in increased δ‐catenin immunoreactivity. δ‐Catenin immunoreactivity increased and turnover decreased when neurons were treated with proteosome inhibitor ALLN, suggesting that δ‐catenin stability is regulated by ubiquitin‐dependent proteolysis. Immunoprecipitation experiments using cells overexpressing δ‐catenin revealed enhanced GSK‐3 β and β ‐catenin interactions. Cells overexpressing δ‐catenin showed additional β ‐catenin ubiquitinated forms and enhanced β ‐catenin turnover. The results identify δ‐catenin as a member of GSK‐3 β signaling potentially promoting the interaction, ubiquitination and turnover of β ‐catenin. Supported by NIA AG026630 and NCI CA111891