ZFIN ID: ZDB-PUB-140210-36
Wnt5a uses CD146 as a receptor to regulate cell motility and convergent extension
Ye, Z., Zhang, C., Tu, T., Sun, M., Liu, D., Lu, D., Feng, J., Yang, D., Liu, F., and Yan, X.
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.