PUBLICATION

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.
Abstract

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.

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