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Nuclear localization is required for Dishevelled function in Wnt/beta-catenin signaling
Keiji Itoh1, Barbara K Brott, Gyu-Un Bae
1Department of Microbiology and Molecular Genetics, Harvard Medical School, and Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Journal of Biology
|February 22, 2005
Summary
Nuclear localization of Dishevelled (Dsh) protein is essential for its role in the Wnt/beta-catenin signaling pathway. Dsh accumulates in the nucleus upon Wnt stimulation, indicating its importance in this developmental process.
Area of Science:
- Developmental Biology
- Cell Signaling
- Molecular Biology
Background:
- Dishevelled (Dsh) is crucial for Wnt/Frizzled signaling in embryonic development.
- The role of Dsh's subcellular localization in signaling is not well understood.
Purpose of the Study:
- To investigate the importance of Dishevelled (Dsh) subcellular localization for Wnt signaling.
- To determine if nuclear localization of Dsh is required for its function.
Main Methods:
- Mutagenesis of the nuclear-export signal (NES) in Dsh.
- Inhibiting nuclear export in Xenopus and mammalian cells.
- Assessing Dsh activity in canonical Wnt signaling.
Main Results:
- Disrupting the NES or inhibiting nuclear export causes Dsh nuclear accumulation.
- Mutations preventing nuclear localization impair Dsh signaling activity.
- Wnt3a stimulation leads to endogenous Dsh nuclear accumulation in cells.
Conclusions:
- Nuclear localization of Dsh is necessary for its function in the canonical Wnt/beta-catenin pathway.
- Findings support models of Wnt signal transduction involving nuclear Dsh.