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Assembly of Dishevelled 3-based supermolecular complexes via phosphorylation and Axin
Noriko Yokoyama1, Nelli G Markova, Hsien-Yu Wang
1Departments of Pharmacology, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY, 11794-8651, USA. noriko@pharm.stonybrook.edu.
Journal of Molecular Signaling
|July 4, 2012
Summary
Wnt3a signaling requires Dishevelled-3 (Dvl3) phosphorylation and Axin to form large supermolecular complexes, which are essential for activating downstream gene transcription.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Dishevelled-3 (Dvl3) acts as a crucial scaffold in Wnt signaling pathways.
- Dvl3 polymerizes into dynamic aggregates called 'signalsomes' in the canonical Wnt/β-catenin pathway.
- These signalsomes transmit signals from the Frizzled receptor to downstream components.
Purpose of the Study:
- To investigate the roles of Dvl3 phosphorylation and Axin in the assembly of Dvl3-based supermolecular complexes.
- To understand the molecular requirements for Wnt3a-induced signal propagation in totipotent mouse F9 teratocarcinoma cells.
Main Methods:
- Steric-exclusion chromatography
- Affinity pull-downs
- Proteomics
- Fluorescence correlation microscopy (FCS)
- Site-directed mutagenesis of Dvl3 and Axin
Main Results:
- Wnt3a stimulation induces the formation of very large Dvl3-based supermolecular complexes.
- Phosphorylation site mutations on Dvl3 disrupt signalsome assembly and Wnt3a-induced transcription.
- Axin is essential for organizing these complexes; its depletion or mutation blocks assembly.
Conclusions:
- Wnt3a activation of the canonical Wnt pathway necessitates Dvl3 phosphorylation and Axin.
- The assembly of large, Dvl3-based supermolecular complexes is a prerequisite for Lef/Tcf-sensitive transcription.
- These findings elucidate key molecular events in Wnt signal transduction.
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