Wnt5a uses CD146 as a receptor to regulate cell motility and convergent extension，Nature Communications 4, 13 December 2013

Nature Communications 4, Article number: 2803 doi:10.1038/ncomms3803

Wnt5a uses CD146 as a receptor to regulate cell motility and convergent extension

Zhongde Ye, Chunxia Zhang, Tao Tu, Min Sun, Dan Liu, Di Lu, Jing Feng, Dongling Yang, Feng Liu & Xiyun Yan

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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文章链接：http://www.nature.com/ncomms/2013/131213/ncomms3803/full/ncomms3803.html