Destruction complex dynamics: Wnt/β-catenin signaling alters Axin-GSK3β interactions in vivo
| Autor: | Jessie May Laumann, Misha Naiman, Daniel B. Lybrand, Gregory D. Scott, Samuel Petshow, Kevin Hansen, Mitzi Boardman, Marcel Wehrli |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Conformational change
Protein Folding Embryo Nonmammalian Protein Conformation Regulator Biology Animals Genetically Modified 03 medical and health sciences Bimolecular fluorescence complementation 0302 clinical medicine Axin Protein In vivo medicine Animals Drosophila Proteins Phosphorylation Molecular Biology Wnt Signaling Pathway beta Catenin 030304 developmental biology Body Patterning 0303 health sciences Axin Signaling Complex Glycogen Synthase Kinase 3 beta Tumor Suppressor Proteins Genetic Complementation Test Optical Imaging Wnt signaling pathway Cell biology Wnt Proteins medicine.anatomical_structure Drosophila melanogaster Cytoplasm Signal transduction Nucleus 030217 neurology & neurosurgery Developmental Biology Research Article Protein Binding |
| Zdroj: | Development |
| Popis: | The central regulator of the Wnt/β-catenin pathway is the Axin/APC/GSK3β destruction complex (DC), which in unstimulated conditions targets cytoplasmic β-catenin for degradation. How Wnt activation inhibits the DC to permit β-catenin-dependent signaling remains controversial, in part because the DC and its regulation have never been observed in vivo. Using Bimolecular Fluorescence Complementation (BiFC) methods, we have now analyzed the activity of the DC under near-physiological conditions in Drosophila. By focusing on well-established patterns of Wnt/Wg signaling in the developing Drosophila wing, we have defined the sequence of events by which activated Wnt receptors induce a conformational change within the DC, resulting in modified Axin-GSK3β interactions that prevent β-catenin degradation. Surprisingly, the nucleus is surrounded by active DCs, which principally control β-catenin's degradation and thereby nuclear access. These DCs are inactivated and removed upon Wnt signal transduction. These results suggest a novel mechanistic model for dynamic Wnt signaling transduction in vivo. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|