Wnt5a uses CD146 as a receptor to regulate cell motility and convergent extension
- Authors
- Ye, Z., Zhang, C., Tu, T., Sun, M., Liu, D., Lu, D., Feng, J., Yang, D., Liu, F., and Yan, X.
- ID
- ZDB-PUB-140210-36
- Date
- 2013
- Source
- Nature communications 4: 2803 (Journal)
- Registered Authors
- Liu, Feng
- Keywords
- none
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing/metabolism
- Animals
- CD146 Antigen/metabolism
- Cell Movement*/physiology
- Cell Polarity*
- Gastrulation*
- HEK293 Cells
- HT29 Cells
- Human Umbilical Vein Endothelial Cells
- Humans
- JNK Mitogen-Activated Protein Kinases/metabolism
- Phosphoproteins/metabolism
- Proto-Oncogene Proteins/metabolism*
- Wnt Proteins/metabolism*
- Wnt Signaling Pathway
- Zebrafish
- beta Catenin/metabolism
- PubMed
- 24335906 Full text @ Nat. Commun.
Dysregulation of Wnt signalling leads to developmental defects and diseases. Non-canonical Wnt signalling via planar cell polarity proteins regulates cell migration and convergent extension; however, the underlying mechanisms are poorly understood. Here we report that Wnt5a uses CD146 as a receptor to regulate cell migration and zebrafish embryonic convergent extension. CD146 binds to Wnt5a with the high affinity required for Wnt5a-induced activation of Dishevelled (Dvl) and c-jun amino-terminal kinase (JNK). The interaction between CD146 and Dvl2 is enhanced on Wnt5a treatment. Mutation of the Dvl2-binding region impairs its ability to activate JNK, promote cell migration and facilitate the formation of cell protrusions. Knockdown of Dvls impairs CD146-induced cell migration. Interestingly, CD146 inhibits canonical Wnt signalling by promoting β-catenin degradation. Our results suggest a model in which CD146 acts as a functional Wnt5a receptor in regulating cell migration and convergent extension, turning off the canonical Wnt signalling branch.