PUBLICATION
In vivo analysis of formation and endocytosis of the Wnt/β-Catenin signaling complex in zebrafish embryos
- Authors
- Hagemann, A.I., Kurz, J., Kauffeld, S., Chen, Q., Reeves, P.M., Weber, S., Schindler, S., Davidson, G., Kirchhausen, T., Scholpp, S.
- ID
- ZDB-PUB-140731-2
- Date
- 2014
- Source
- Journal of Cell Science 127(Pt 18): 3970-82 (Journal)
- Registered Authors
- Hagemann, Anja, Schindler, Simone, Scholpp, Steffen, Weber, Sabrina
- Keywords
- none
- MeSH Terms
-
- Adaptor Protein Complex 2/genetics
- Adaptor Protein Complex 2/metabolism
- Adaptor Protein Complex mu Subunits/genetics
- Adaptor Protein Complex mu Subunits/metabolism
- Adaptor Proteins, Signal Transducing/genetics
- Adaptor Proteins, Signal Transducing/metabolism
- Animals
- Endocytosis*
- Female
- Low Density Lipoprotein Receptor-Related Protein-6/genetics
- Low Density Lipoprotein Receptor-Related Protein-6/metabolism
- Multiprotein Complexes/genetics
- Multiprotein Complexes/metabolism*
- Phosphoproteins/genetics
- Phosphoproteins/metabolism
- Protein Binding
- Wnt Signaling Pathway*
- Xenopus/embryology
- Xenopus/genetics
- Xenopus/metabolism*
- beta Catenin/metabolism*
- PubMed
- 25074807 Full text @ J. Cell Sci.
Citation
Hagemann, A.I., Kurz, J., Kauffeld, S., Chen, Q., Reeves, P.M., Weber, S., Schindler, S., Davidson, G., Kirchhausen, T., Scholpp, S. (2014) In vivo analysis of formation and endocytosis of the Wnt/β-Catenin signaling complex in zebrafish embryos. Journal of Cell Science. 127(Pt 18):3970-82.
Abstract
After activation by Wnt/β-Catenin ligands, a multi-protein complex assembles at the clustering membrane-bound receptors and intracellular signal transducers into the so-called Lrp6-signalosome. However, the mechanism of signalosome formation and dissolution is yet not clear. Our imaging studies of live zebrafish embryos show that the signalosome is a highly dynamic structure. It is continuously assembled by Dvl2-mediated recruitment of the transducer complex to the activated receptors and partially disassembled by endocytosis. We find that, after internalization, the ligand-receptor complex and the transducer complex take separate routes. The Wnt-Fz-Lrp6 complex follows a Rab-positive endocytic path. However, when still bound to the transducer complex, Dvl2 forms intracellular aggregates. We show that this endocytic process is not only essential for ligand-receptor internalization but also for signaling. The μ2-subunit of the endocytic Clathrin adaptor Ap2 interacts with Dvl2 to maintain its stability during endocytosis. Blockage of Ap2μ2 function leads to Dvl2 degradation, inhibiton of signalosome formation at the plasma membrane and, consequently, reduction of signaling. We conclude that Ap2μ2-mediated endocytosis is important to maintain Wnt/β-catenin signaling in vertebrates.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping