Wnt5a 通过 CD146 作为受体来调节细胞迁移和会聚延伸。
Wnt5a uses CD146 as a receptor to regulate cell motility and convergent extension.
机构信息
Key Laboratory of Protein and Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
出版信息
Nat Commun. 2013;4:2803. doi: 10.1038/ncomms3803.
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.
Wnt 信号通路的失调会导致发育缺陷和疾病。平面细胞极性蛋白的非经典 Wnt 信号通路调节细胞迁移和会聚延伸；然而，其潜在的机制还知之甚少。在这里，我们报告 Wnt5a 使用 CD146 作为受体来调节细胞迁移和斑马鱼胚胎的会聚延伸。CD146 与 Wnt5a 结合的亲和力很高，足以激活 Dvl（Dishevelled）和 c-jun 氨基末端激酶（JNK）。在 Wnt5a 处理后，CD146 和 Dvl2 之间的相互作用增强。Dvl2 结合区域的突变会损害其激活 JNK、促进细胞迁移和促进细胞突起形成的能力。Dvls 的敲低会损害 CD146 诱导的细胞迁移。有趣的是，CD146 通过促进 β-连环蛋白降解来抑制经典的 Wnt 信号通路。我们的结果提出了一个模型，即 CD146 作为功能性 Wnt5a 受体在调节细胞迁移和会聚延伸中起作用，关闭经典的 Wnt 信号通路分支。
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